Anemia, Kidney Disease
Conditions
Keywords
anemia, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, erythropoietin, safety, efficacy, tolerability, pharmacokinetics
Brief summary
The purpose of this study is to evaluate the dose response (efficacy), pharmacodynamic response, pharmacokinetics, safety, and tolerability of orally administered AKB-6548 in pre-dialysis participants with anemia with repeat dosing for 42 days.
Interventions
DRUGAKB-6548
oral dose administered once daily for 42 days
DRUGPlacebo
oral Placebo administered once daily for 42 days
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18 to 79 years of age, inclusive * Chronic Kidney Disease (eGFR \<60 mL/min), not yet on dialysis * Hemoglobin (Hgb) ≤ 10.5 g/dL * Transferring saturation ≥ 20% * Ferritin ≥ 50 ng/mL Key
Exclusion criteria
* Body mass index \>42 * Red blood cell transfusion within 12 weeks * Androgen therapy within the previous 21 days prior to study dosing * Therapy with any approved or experimental erythropoiesis stimulating agent (ESA) within the 11 weeks prior to the Screening visit * Participants meeting the criteria of ESA resistance within the previous 4 months * Individual doses of intravenous iron of greater than 250 mg within the past 21 days * Aspartate aminotransferase or alanine aminotransferase \>1.8x upper limit of normal (ULN) * Alkaline phosphatase \>2x ULN * Total bilirubin \>1.5x ULN * Uncontrolled hypertension * New York Heart Association Class III or IV congestive heart failure * Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Baseline, Week 6 | Absolute change from Baseline was calculated as the Week 6 (end of treatment) value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing. If there was only one measurement prior to dosing, this measurement served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased. |
| Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated HCT concentration increased. |
| Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated RBC count increased. |
| Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte count increased. |
| Maximum Change From Baseline in Hgb | Baseline; up to Week 8 | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased. |
| Maximum Change From Baseline in HCT | Baseline; up to Week 8 | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that HCT concentration increased. |
| Maximum Change From Baseline in RBC Count | Baseline; up to Week 8 | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that RBC count increased. |
| Maximum Change in Absolute Reticulocyte Count From Baseline | Baseline; up to Week 8 | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline absolute reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that reticulocyte count increased. |
| Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Up to Week 6 (End of the Dosing Period) | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | Up to Week 6 (End of The Dosing Period) | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | Up to Week 6 (End of The Dosing Period) | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | Up to Week 6 (End of The Dosing Period) | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Up to Week 6 (End of The Dosing Period) | Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline reticulocytes count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Change From Baseline in Reticulocyte Hgb Content at Week 6 | Baseline, Week 6 | Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte Hgb content increased. |
| Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Unsaturated Iron Binding Capacity was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron saturation was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline erythropoietin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Change From Baseline in Hepcidin at Week 6 | Baseline, Week 6 | Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline hepcidin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
| Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2: Pre-dose and post-dose; Week 4: Pre-dose | Plasma samples were collected for the analysis. |
| Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 2: Pre-dose; Week 4: Pre-dose | Plasma samples were collected for the analysis. |
| Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Week 8 (Follow-up Visit 2 weeks after last dose) | An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. A TEAE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. A SAE included AEs that met one or more of the following criteria/outcomes: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter | Up to Week 8 (Follow-up Visit 2 weeks after last dose) | Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings | Up to Week 8 (Follow-up Visit 2 weeks after last dose) | A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. Clinical significance is determined by the investigator. The investigator was responsible for reviewing laboratory results for clinical significance. |
| Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline, Week 6 | A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected). |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | Up to Week 8 (Follow-up Visit 2 weeks after last dose) | Parameters assessed for laboratory values included hematology, serum chemistry, C-reactive protein, DHEA-S, VEGF, and cystatin C. The investigator was responsible for reviewing laboratory results for clinically significant changes. |
| Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8) | Change from Baseline was calculated as the visit value minus the Baseline value. Baseline total iron was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. |
Countries
United States
Participant flow
Pre-assignment details
A total of 93 participants were enrolled and randomized into the study. Only 91 participants received the treatment.
Participants by arm
| Arm | Count |
|---|---|
| AKB-6548 240 mg Participants with anemia secondary to chronic kidney disease (CKD), stages 3 and 4 were administered with an oral dose of AKB-6548 240 milligrams (mg) capsule once daily (QD) for 42 days. | 18 |
| AKB-6548 370 mg Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 370 mg capsule QD for 42 days. | 18 |
| AKB-6548 500 mg Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 500 mg capsule QD for 42 days. | 17 |
| AKB-6548 630 mg Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of AKB-6548 630 mg capsule QD for 42 days. | 19 |
| Placebo Participants with anemia secondary to CKD, stages 3 and 4 were administered with an oral dose of matching Placebo QD for 42 days. | 19 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Participant given Aranesp injection | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal of informed consent | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | AKB-6548 370 mg | AKB-6548 500 mg | AKB-6548 630 mg | Placebo | AKB-6548 240 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 68.9 Years STANDARD_DEVIATION 7.84 | 64.7 Years STANDARD_DEVIATION 9.47 | 64.9 Years STANDARD_DEVIATION 8.79 | 64.9 Years STANDARD_DEVIATION 9.97 | 64.2 Years STANDARD_DEVIATION 12.17 | 65.5 Years STANDARD_DEVIATION 9.69 |
| CKD stage Stage 3 | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 23 Participants |
| CKD stage Stage 4 | 14 Participants | 13 Participants | 14 Participants | 14 Participants | 13 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 7 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 13 Participants | 15 Participants | 14 Participants | 11 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 7 Participants | 3 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 13 Participants | 13 Participants | 9 Participants | 14 Participants | 10 Participants | 59 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 7 Participants | 12 Participants | 9 Participants | 48 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 12 Participants | 7 Participants | 9 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 1 / 18 | 0 / 17 | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 9 / 18 | 5 / 18 | 8 / 17 | 11 / 19 | 11 / 19 |
| serious Total, serious adverse events | 2 / 18 | 3 / 18 | 1 / 17 | 1 / 19 | 1 / 19 |
Outcome results
Primary
Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)
Absolute change from Baseline was calculated as the Week 6 (end of treatment) value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing. If there was only one measurement prior to dosing, this measurement served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.
Time frame: Baseline, Week 6
Population: Modified intent-to-treat (MITT) population: All randomized participants who received at least one dose of study medication and had a Baseline (both Screening and Baseline for Hgb and red blood cells \[RBC\] count) and at least one post-baseline measurement. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Baseline | 9.46 Grams per deciliter (g/dL) | Standard Deviation 0.792 |
| AKB-6548 240 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Change from Baseline at Week 6 | 0.77 Grams per deciliter (g/dL) | Standard Deviation 0.665 |
| AKB-6548 370 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Baseline | 9.93 Grams per deciliter (g/dL) | Standard Deviation 0.643 |
| AKB-6548 370 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Change from Baseline at Week 6 | 0.73 Grams per deciliter (g/dL) | Standard Deviation 0.623 |
| AKB-6548 500 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Baseline | 9.86 Grams per deciliter (g/dL) | Standard Deviation 0.606 |
| AKB-6548 500 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Change from Baseline at Week 6 | 1.25 Grams per deciliter (g/dL) | Standard Deviation 0.644 |
| AKB-6548 630 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Change from Baseline at Week 6 | 1.43 Grams per deciliter (g/dL) | Standard Deviation 0.668 |
| AKB-6548 630 mg | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Baseline | 9.67 Grams per deciliter (g/dL) | Standard Deviation 0.796 |
| Placebo | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Baseline | 9.83 Grams per deciliter (g/dL) | Standard Deviation 0.677 |
| Placebo | Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6) | Change from Baseline at Week 6 | -0.03 Grams per deciliter (g/dL) | Standard Deviation 0.649 |
95% CI: [0.24, 1.35]
95% CI: [0.2, 1.33]
95% CI: [0.73, 1.83]
95% CI: [0.91, 2]
p-value: <0.0001ANOVA
Secondary
Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte count increased.
Time frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 0.0766 10^6 cells/μL | Standard Deviation 0.02855 |
| AKB-6548 240 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.0022 10^6 cells/μL | Standard Deviation 0.01279 |
| AKB-6548 240 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.0012 10^6 cells/μL | Standard Deviation 0.01505 |
| AKB-6548 240 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.0029 10^6 cells/μL | Standard Deviation 0.01181 |
| AKB-6548 240 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.0020 10^6 cells/μL | Standard Deviation 0.01736 |
| AKB-6548 240 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -0.0042 10^6 cells/μL | Standard Deviation 0.019 |
| AKB-6548 370 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.0116 10^6 cells/μL | Standard Deviation 0.0239 |
| AKB-6548 370 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.0015 10^6 cells/μL | Standard Deviation 0.02616 |
| AKB-6548 370 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 0.0569 10^6 cells/μL | Standard Deviation 0.01891 |
| AKB-6548 370 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.0196 10^6 cells/μL | Standard Deviation 0.01919 |
| AKB-6548 370 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.0128 10^6 cells/μL | Standard Deviation 0.01586 |
| AKB-6548 370 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.0134 10^6 cells/μL | Standard Deviation 0.01733 |
| AKB-6548 500 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.0234 10^6 cells/μL | Standard Deviation 0.02685 |
| AKB-6548 500 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.0061 10^6 cells/μL | Standard Deviation 0.02217 |
| AKB-6548 500 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 0.0811 10^6 cells/μL | Standard Deviation 0.01993 |
| AKB-6548 500 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.0346 10^6 cells/μL | Standard Deviation 0.01997 |
| AKB-6548 500 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.0259 10^6 cells/μL | Standard Deviation 0.02223 |
| AKB-6548 500 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -0.0152 10^6 cells/μL | Standard Deviation 0.01467 |
| AKB-6548 630 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.0206 10^6 cells/μL | Standard Deviation 0.02369 |
| AKB-6548 630 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.0289 10^6 cells/μL | Standard Deviation 0.03152 |
| AKB-6548 630 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.0292 10^6 cells/μL | Standard Deviation 0.01625 |
| AKB-6548 630 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -0.0119 10^6 cells/μL | Standard Deviation 0.02494 |
| AKB-6548 630 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.0047 10^6 cells/μL | Standard Deviation 0.02639 |
| AKB-6548 630 mg | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 0.0674 10^6 cells/μL | Standard Deviation 0.02715 |
| Placebo | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.0004 10^6 cells/μL | Standard Deviation 0.01788 |
| Placebo | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -0.0015 10^6 cells/μL | Standard Deviation 0.01091 |
| Placebo | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.0010 10^6 cells/μL | Standard Deviation 0.01677 |
| Placebo | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -0.0035 10^6 cells/μL | Standard Deviation 0.01522 |
| Placebo | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -0.0023 10^6 cells/μL | Standard Deviation 0.01636 |
| Placebo | Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 0.0700 10^6 cells/μL | Standard Deviation 0.03319 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =12 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.00552 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.00092 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.97222 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =12 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00082 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.65792 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.41022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00232 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00522 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00172 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.73782 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.33712 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.09162 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.46562 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.16292 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.70322 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.51942 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.85162 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00172 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.06562 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.64952 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline erythropoietin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)
Population: Intent-to-treat (ITT) population: All randomized participants who received at least one dose of study medication. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -3.538 ng/mL | Standard Deviation 20.3172 |
| AKB-6548 240 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -3.853 ng/mL | Standard Deviation 15.1335 |
| AKB-6548 240 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -3.050 ng/mL | Standard Deviation 15.1756 |
| AKB-6548 240 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 18.011 ng/mL | Standard Deviation 56.3608 |
| AKB-6548 370 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -0.563 ng/mL | Standard Deviation 5.5372 |
| AKB-6548 370 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.606 ng/mL | Standard Deviation 3.207 |
| AKB-6548 370 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -1.013 ng/mL | Standard Deviation 3.9836 |
| AKB-6548 370 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 4.339 ng/mL | Standard Deviation 4.1462 |
| AKB-6548 500 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 1.142 ng/mL | Standard Deviation 11.8961 |
| AKB-6548 500 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 7.287 ng/mL | Standard Deviation 8.8333 |
| AKB-6548 500 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -2.061 ng/mL | Standard Deviation 6.2689 |
| AKB-6548 500 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -3.329 ng/mL | Standard Deviation 5.9821 |
| AKB-6548 630 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -2.483 ng/mL | Standard Deviation 9.5483 |
| AKB-6548 630 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 8.826 ng/mL | Standard Deviation 10.2773 |
| AKB-6548 630 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -4.844 ng/mL | Standard Deviation 9.4601 |
| AKB-6548 630 mg | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.372 ng/mL | Standard Deviation 14.4615 |
| Placebo | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -2.650 ng/mL | Standard Deviation 8.2146 |
| Placebo | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -0.850 ng/mL | Standard Deviation 9.337 |
| Placebo | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -1.492 ng/mL | Standard Deviation 10.1597 |
| Placebo | Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 6.963 ng/mL | Standard Deviation 14.1425 |
Secondary
Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -65.5 Nanograms per milliliter (ng/mL) | Standard Deviation 115.89 |
| AKB-6548 240 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 349.5 Nanograms per milliliter (ng/mL) | Standard Deviation 226.27 |
| AKB-6548 240 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -50.4 Nanograms per milliliter (ng/mL) | Standard Deviation 91.22 |
| AKB-6548 240 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -66.0 Nanograms per milliliter (ng/mL) | Standard Deviation 67.72 |
| AKB-6548 240 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -69.8 Nanograms per milliliter (ng/mL) | Standard Deviation 101.67 |
| AKB-6548 370 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -59.4 Nanograms per milliliter (ng/mL) | Standard Deviation 58.76 |
| AKB-6548 370 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -48.7 Nanograms per milliliter (ng/mL) | Standard Deviation 63.08 |
| AKB-6548 370 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -41.7 Nanograms per milliliter (ng/mL) | Standard Deviation 53.18 |
| AKB-6548 370 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -37.7 Nanograms per milliliter (ng/mL) | Standard Deviation 73.31 |
| AKB-6548 370 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 245.8 Nanograms per milliliter (ng/mL) | Standard Deviation 215.18 |
| AKB-6548 500 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -89.6 Nanograms per milliliter (ng/mL) | Standard Deviation 138.8 |
| AKB-6548 500 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 332.3 Nanograms per milliliter (ng/mL) | Standard Deviation 330.81 |
| AKB-6548 500 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -72.0 Nanograms per milliliter (ng/mL) | Standard Deviation 75.89 |
| AKB-6548 500 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -88.9 Nanograms per milliliter (ng/mL) | Standard Deviation 64.66 |
| AKB-6548 500 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -86.1 Nanograms per milliliter (ng/mL) | Standard Deviation 67.75 |
| AKB-6548 630 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -27.4 Nanograms per milliliter (ng/mL) | Standard Deviation 107.42 |
| AKB-6548 630 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 240.2 Nanograms per milliliter (ng/mL) | Standard Deviation 142.1 |
| AKB-6548 630 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -86.6 Nanograms per milliliter (ng/mL) | Standard Deviation 62.73 |
| AKB-6548 630 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -80.6 Nanograms per milliliter (ng/mL) | Standard Deviation 64.5 |
| AKB-6548 630 mg | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -58.9 Nanograms per milliliter (ng/mL) | Standard Deviation 54.72 |
| Placebo | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -20.5 Nanograms per milliliter (ng/mL) | Standard Deviation 39.24 |
| Placebo | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -19.6 Nanograms per milliliter (ng/mL) | Standard Deviation 41.72 |
| Placebo | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 200.8 Nanograms per milliliter (ng/mL) | Standard Deviation 115.99 |
| Placebo | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -20.2 Nanograms per milliliter (ng/mL) | Standard Deviation 39.35 |
| Placebo | Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -12.9 Nanograms per milliliter (ng/mL) | Standard Deviation 35.49 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00922 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00122 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.11572 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00692 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00342 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00672 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.04012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00422 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.04222 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.02322 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.02432 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.10892 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.08332 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated HCT concentration increased.
Time frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 29.0 Percentage of red blood cells in blood | Standard Deviation 2.57 |
| AKB-6548 240 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.5 Percentage of red blood cells in blood | Standard Deviation 2.28 |
| AKB-6548 240 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.2 Percentage of red blood cells in blood | Standard Deviation 2.46 |
| AKB-6548 240 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 1.7 Percentage of red blood cells in blood | Standard Deviation 2.37 |
| AKB-6548 240 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 1.8 Percentage of red blood cells in blood | Standard Deviation 2.71 |
| AKB-6548 240 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 1.9 Percentage of red blood cells in blood | Standard Deviation 2.3 |
| AKB-6548 370 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 2.1 Percentage of red blood cells in blood | Standard Deviation 2.46 |
| AKB-6548 370 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.7 Percentage of red blood cells in blood | Standard Deviation 1.9 |
| AKB-6548 370 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 29.6 Percentage of red blood cells in blood | Standard Deviation 2.45 |
| AKB-6548 370 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.1 Percentage of red blood cells in blood | Standard Deviation 1.59 |
| AKB-6548 370 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.6 Percentage of red blood cells in blood | Standard Deviation 1.67 |
| AKB-6548 370 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.2 Percentage of red blood cells in blood | Standard Deviation 1.87 |
| AKB-6548 500 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 3.1 Percentage of red blood cells in blood | Standard Deviation 2.59 |
| AKB-6548 500 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 3.4 Percentage of red blood cells in blood | Standard Deviation 2.47 |
| AKB-6548 500 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 30.4 Percentage of red blood cells in blood | Standard Deviation 2.41 |
| AKB-6548 500 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 1.6 Percentage of red blood cells in blood | Standard Deviation 2.33 |
| AKB-6548 500 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 1.2 Percentage of red blood cells in blood | Standard Deviation 1.25 |
| AKB-6548 500 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 2.4 Percentage of red blood cells in blood | Standard Deviation 2.62 |
| AKB-6548 630 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 3.4 Percentage of red blood cells in blood | Standard Deviation 3.52 |
| AKB-6548 630 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 1.6 Percentage of red blood cells in blood | Standard Deviation 2.65 |
| AKB-6548 630 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 1.5 Percentage of red blood cells in blood | Standard Deviation 2.04 |
| AKB-6548 630 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 2.8 Percentage of red blood cells in blood | Standard Deviation 3.44 |
| AKB-6548 630 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 4.3 Percentage of red blood cells in blood | Standard Deviation 2.74 |
| AKB-6548 630 mg | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 29.6 Percentage of red blood cells in blood | Standard Deviation 3.68 |
| Placebo | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.4 Percentage of red blood cells in blood | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.3 Percentage of red blood cells in blood | Standard Deviation 2.06 |
| Placebo | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.2 Percentage of red blood cells in blood | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.0 Percentage of red blood cells in blood | Standard Deviation 2.78 |
| Placebo | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.1 Percentage of red blood cells in blood | Standard Deviation 2.34 |
| Placebo | Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 29.8 Percentage of red blood cells in blood | Standard Deviation 1.96 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.52192 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.67432 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.00782 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.03012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.45022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.69672 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.73852 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.01762 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00572 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.55512 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00862 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.23852 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00072 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.88952 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.01272 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00762 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00072 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.55222 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00312 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.21882 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00542 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00372 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.95212 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Hepcidin at Week 6
Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline hepcidin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 6
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Hepcidin at Week 6 | Baseline | 326.35 ng/mL | Standard Deviation 222.037 |
| AKB-6548 240 mg | Change From Baseline in Hepcidin at Week 6 | Change from Baseline at Week 6 | -28.64 ng/mL | Standard Deviation 185.263 |
| AKB-6548 370 mg | Change From Baseline in Hepcidin at Week 6 | Baseline | 241.03 ng/mL | Standard Deviation 158.871 |
| AKB-6548 370 mg | Change From Baseline in Hepcidin at Week 6 | Change from Baseline at Week 6 | -90.91 ng/mL | Standard Deviation 106.826 |
| AKB-6548 500 mg | Change From Baseline in Hepcidin at Week 6 | Baseline | 242.51 ng/mL | Standard Deviation 117.326 |
| AKB-6548 500 mg | Change From Baseline in Hepcidin at Week 6 | Change from Baseline at Week 6 | -85.01 ng/mL | Standard Deviation 45.864 |
| AKB-6548 630 mg | Change From Baseline in Hepcidin at Week 6 | Change from Baseline at Week 6 | -144.90 ng/mL | Standard Deviation 184.64 |
| AKB-6548 630 mg | Change From Baseline in Hepcidin at Week 6 | Baseline | 282.75 ng/mL | Standard Deviation 239.266 |
| Placebo | Change From Baseline in Hepcidin at Week 6 | Baseline | 258.29 ng/mL | Standard Deviation 144.115 |
| Placebo | Change From Baseline in Hepcidin at Week 6 | Change from Baseline at Week 6 | -32.54 ng/mL | Standard Deviation 103.937 |
p-value: =0.54562 sided t-test/Wilcoxon Signed-rank Test
p-value: =0.00532 sided t-test/Wilcoxon Signed-rank Test
p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
p-value: =0.0042 sided t-test/Wilcoxon Signed-rank Test
p-value: =0.20172 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.
Time frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 9.46 g/dL | Standard Deviation 0.792 |
| AKB-6548 240 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.06 g/dL | Standard Deviation 0.559 |
| AKB-6548 240 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.16 g/dL | Standard Deviation 0.575 |
| AKB-6548 240 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.54 g/dL | Standard Deviation 0.659 |
| AKB-6548 240 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.77 g/dL | Standard Deviation 0.665 |
| AKB-6548 240 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.78 g/dL | Standard Deviation 0.685 |
| AKB-6548 370 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.73 g/dL | Standard Deviation 0.623 |
| AKB-6548 370 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.40 g/dL | Standard Deviation 0.553 |
| AKB-6548 370 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 9.93 g/dL | Standard Deviation 0.643 |
| AKB-6548 370 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.00 g/dL | Standard Deviation 0.59 |
| AKB-6548 370 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.36 g/dL | Standard Deviation 0.605 |
| AKB-6548 370 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | -0.12 g/dL | Standard Deviation 0.452 |
| AKB-6548 500 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.85 g/dL | Standard Deviation 0.65 |
| AKB-6548 500 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 1.25 g/dL | Standard Deviation 0.644 |
| AKB-6548 500 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 9.86 g/dL | Standard Deviation 0.606 |
| AKB-6548 500 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.54 g/dL | Standard Deviation 0.586 |
| AKB-6548 500 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.28 g/dL | Standard Deviation 0.439 |
| AKB-6548 500 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 1.04 g/dL | Standard Deviation 0.848 |
| AKB-6548 630 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 1.06 g/dL | Standard Deviation 0.9 |
| AKB-6548 630 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.29 g/dL | Standard Deviation 0.622 |
| AKB-6548 630 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.53 g/dL | Standard Deviation 0.455 |
| AKB-6548 630 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 1.01 g/dL | Standard Deviation 0.872 |
| AKB-6548 630 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 1.43 g/dL | Standard Deviation 0.668 |
| AKB-6548 630 mg | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 9.67 g/dL | Standard Deviation 0.796 |
| Placebo | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.03 g/dL | Standard Deviation 0.649 |
| Placebo | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.14 g/dL | Standard Deviation 0.654 |
| Placebo | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.04 g/dL | Standard Deviation 0.531 |
| Placebo | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.06 g/dL | Standard Deviation 0.877 |
| Placebo | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.08 g/dL | Standard Deviation 0.613 |
| Placebo | Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 9.83 g/dL | Standard Deviation 0.677 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.93552 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.65942 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.02032 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.03692 sided t-test/Wilcoxon Signed-rank Test
p-value: =0.37132 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.1632 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.76152 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.0042 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00032 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.39782 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00832 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.03232 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00032 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.4232 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00232 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00092 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.52912 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.02222 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.93142 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron saturation was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.3 Percentage of saturation | Standard Deviation 9.24 |
| AKB-6548 240 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 30.4 Percentage of saturation | Standard Deviation 7.56 |
| AKB-6548 240 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -4.1 Percentage of saturation | Standard Deviation 7.08 |
| AKB-6548 240 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -1.5 Percentage of saturation | Standard Deviation 6.26 |
| AKB-6548 240 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -1.9 Percentage of saturation | Standard Deviation 8.1 |
| AKB-6548 370 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -3.8 Percentage of saturation | Standard Deviation 6.36 |
| AKB-6548 370 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -2.3 Percentage of saturation | Standard Deviation 7 |
| AKB-6548 370 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -3.8 Percentage of saturation | Standard Deviation 7.34 |
| AKB-6548 370 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -3.9 Percentage of saturation | Standard Deviation 8.9 |
| AKB-6548 370 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 32.4 Percentage of saturation | Standard Deviation 9.82 |
| AKB-6548 500 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -3.7 Percentage of saturation | Standard Deviation 7.91 |
| AKB-6548 500 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 31.4 Percentage of saturation | Standard Deviation 13.35 |
| AKB-6548 500 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 1.4 Percentage of saturation | Standard Deviation 9.15 |
| AKB-6548 500 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -2.3 Percentage of saturation | Standard Deviation 7.69 |
| AKB-6548 500 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.5 Percentage of saturation | Standard Deviation 9.94 |
| AKB-6548 630 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 1.6 Percentage of saturation | Standard Deviation 9.27 |
| AKB-6548 630 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 26.5 Percentage of saturation | Standard Deviation 10.17 |
| AKB-6548 630 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -4.6 Percentage of saturation | Standard Deviation 6.44 |
| AKB-6548 630 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -0.2 Percentage of saturation | Standard Deviation 6.52 |
| AKB-6548 630 mg | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.6 Percentage of saturation | Standard Deviation 8.81 |
| Placebo | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -0.2 Percentage of saturation | Standard Deviation 8.65 |
| Placebo | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -2.1 Percentage of saturation | Standard Deviation 9.09 |
| Placebo | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 27.7 Percentage of saturation | Standard Deviation 6.6 |
| Placebo | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 1.2 Percentage of saturation | Standard Deviation 5.8 |
| Placebo | Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -0.9 Percentage of saturation | Standard Deviation 7.86 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.27562 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.14142 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.69412 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.39532 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.0852 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.60452 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.77432 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.53262 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.34652 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.94032 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.8312 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.06542 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.41692 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.01032 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.39682 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.03252 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.21512 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.84362 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.59622 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.39572 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated RBC count increased.
Time frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 3.21 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.415 |
| AKB-6548 240 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | -0.01 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.185 |
| AKB-6548 240 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.02 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.183 |
| AKB-6548 240 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.16 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.213 |
| AKB-6548 240 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.17 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.243 |
| AKB-6548 240 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.24 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.242 |
| AKB-6548 370 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.18 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.273 |
| AKB-6548 370 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.06 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.199 |
| AKB-6548 370 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 3.38 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.286 |
| AKB-6548 370 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -0.05 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.186 |
| AKB-6548 370 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.01 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.202 |
| AKB-6548 370 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | -0.07 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.178 |
| AKB-6548 500 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.26 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.251 |
| AKB-6548 500 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.39 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.252 |
| AKB-6548 500 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 3.37 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.286 |
| AKB-6548 500 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.14 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.229 |
| AKB-6548 500 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.09 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.187 |
| AKB-6548 500 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.30 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.248 |
| AKB-6548 630 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.27 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.294 |
| AKB-6548 630 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | 0.04 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.227 |
| AKB-6548 630 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.11 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.172 |
| AKB-6548 630 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.26 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.273 |
| AKB-6548 630 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.41 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.243 |
| AKB-6548 630 mg | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 3.25 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.366 |
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -0.02 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.223 |
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 0.03 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.281 |
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 1 | -0.02 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.231 |
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.01 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.29 |
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 0.02 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.229 |
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 3.34 10^6 cells/microliter (10^6 cells/μL) | Standard Deviation 0.463 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.39432 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.20962 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.06372 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.50162 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 1).p-value: =0.75492 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.59912 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.42582 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.03362 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.02582 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.24122 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00312 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.77052 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00242 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00062 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.61892 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00752 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.02592 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.88982 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.0012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.28642 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.00162 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.96972 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Reticulocyte Hgb Content at Week 6
Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte Hgb content increased.
Time frame: Baseline, Week 6
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Baseline | 31.02 Picogram | Standard Deviation 2.945 |
| AKB-6548 240 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Change From Baseline at Week 6 | 0.37 Picogram | Standard Deviation 0.971 |
| AKB-6548 370 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Baseline | 31.44 Picogram | Standard Deviation 2.257 |
| AKB-6548 370 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Change From Baseline at Week 6 | 0.29 Picogram | Standard Deviation 0.742 |
| AKB-6548 500 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Baseline | 30.26 Picogram | Standard Deviation 2.605 |
| AKB-6548 500 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Change From Baseline at Week 6 | 0.06 Picogram | Standard Deviation 0.964 |
| AKB-6548 630 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Change From Baseline at Week 6 | 0.15 Picogram | Standard Deviation 1.214 |
| AKB-6548 630 mg | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Baseline | 31.54 Picogram | Standard Deviation 2.575 |
| Placebo | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Baseline | 30.73 Picogram | Standard Deviation 2.634 |
| Placebo | Change From Baseline in Reticulocyte Hgb Content at Week 6 | Change From Baseline at Week 6 | 0.03 Picogram | Standard Deviation 1.104 |
Comparison: p-value was based on the comparison within treatment group.p-value: =0.20652 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.18072 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.78692 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.47432 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.64072 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline total iron was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 3.6 Micrograms per deciliter (µg/dL) | Standard Deviation 23.26 |
| AKB-6548 240 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 66.0 Micrograms per deciliter (µg/dL) | Standard Deviation 18.68 |
| AKB-6548 240 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -7.4 Micrograms per deciliter (µg/dL) | Standard Deviation 19.25 |
| AKB-6548 240 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -1.8 Micrograms per deciliter (µg/dL) | Standard Deviation 15.87 |
| AKB-6548 240 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -1.5 Micrograms per deciliter (µg/dL) | Standard Deviation 21.62 |
| AKB-6548 370 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 2.8 Micrograms per deciliter (µg/dL) | Standard Deviation 15.44 |
| AKB-6548 370 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 4.0 Micrograms per deciliter (µg/dL) | Standard Deviation 16.36 |
| AKB-6548 370 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -3.7 Micrograms per deciliter (µg/dL) | Standard Deviation 18.96 |
| AKB-6548 370 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -7.5 Micrograms per deciliter (µg/dL) | Standard Deviation 22.9 |
| AKB-6548 370 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 77.8 Micrograms per deciliter (µg/dL) | Standard Deviation 22.47 |
| AKB-6548 500 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -1.6 Micrograms per deciliter (µg/dL) | Standard Deviation 20.49 |
| AKB-6548 500 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 76.1 Micrograms per deciliter (µg/dL) | Standard Deviation 32.01 |
| AKB-6548 500 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 10.9 Micrograms per deciliter (µg/dL) | Standard Deviation 22.93 |
| AKB-6548 500 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 3.7 Micrograms per deciliter (µg/dL) | Standard Deviation 25.19 |
| AKB-6548 500 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.9 Micrograms per deciliter (µg/dL) | Standard Deviation 31.9 |
| AKB-6548 630 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 6.2 Micrograms per deciliter (µg/dL) | Standard Deviation 18.5 |
| AKB-6548 630 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 60.7 Micrograms per deciliter (µg/dL) | Standard Deviation 20.51 |
| AKB-6548 630 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 0.7 Micrograms per deciliter (µg/dL) | Standard Deviation 16.54 |
| AKB-6548 630 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 13.2 Micrograms per deciliter (µg/dL) | Standard Deviation 24.18 |
| AKB-6548 630 mg | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 10.4 Micrograms per deciliter (µg/dL) | Standard Deviation 24.54 |
| Placebo | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -2.2 Micrograms per deciliter (µg/dL) | Standard Deviation 20.47 |
| Placebo | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -8.6 Micrograms per deciliter (µg/dL) | Standard Deviation 25.81 |
| Placebo | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 67.6 Micrograms per deciliter (µg/dL) | Standard Deviation 21.12 |
| Placebo | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 3.4 Micrograms per deciliter (µg/dL) | Standard Deviation 16.05 |
| Placebo | Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -4.1 Micrograms per deciliter (µg/dL) | Standard Deviation 18.55 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.60512 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.51972 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.10732 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.13212 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.43582 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.81092 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.25752 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.83612 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.02942 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.88092 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.49712 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.39942 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.50222 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.99162 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.22922 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.13312 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.55182 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.90322 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.23872 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.42512 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 18.8 µg/dL | Standard Deviation 28.81 |
| AKB-6548 240 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 219.4 µg/dL | Standard Deviation 39.39 |
| AKB-6548 240 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 7.8 µg/dL | Standard Deviation 34.88 |
| AKB-6548 240 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 9.2 µg/dL | Standard Deviation 16.34 |
| AKB-6548 240 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 12.9 µg/dL | Standard Deviation 24.97 |
| AKB-6548 370 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 36.8 µg/dL | Standard Deviation 27.76 |
| AKB-6548 370 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 30.1 µg/dL | Standard Deviation 16.2 |
| AKB-6548 370 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 18.7 µg/dL | Standard Deviation 18.09 |
| AKB-6548 370 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 8.7 µg/dL | Standard Deviation 18.15 |
| AKB-6548 370 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 245.8 µg/dL | Standard Deviation 54.61 |
| AKB-6548 500 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 29.9 µg/dL | Standard Deviation 24.08 |
| AKB-6548 500 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 249.2 µg/dL | Standard Deviation 45.29 |
| AKB-6548 500 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 28.1 µg/dL | Standard Deviation 22.32 |
| AKB-6548 500 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 33.0 µg/dL | Standard Deviation 28.54 |
| AKB-6548 500 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.2 µg/dL | Standard Deviation 25.82 |
| AKB-6548 630 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 10.2 µg/dL | Standard Deviation 30.15 |
| AKB-6548 630 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 231.8 µg/dL | Standard Deviation 36.19 |
| AKB-6548 630 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 50.3 µg/dL | Standard Deviation 27.8 |
| AKB-6548 630 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 50.5 µg/dL | Standard Deviation 28.64 |
| AKB-6548 630 mg | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 31.7 µg/dL | Standard Deviation 28.73 |
| Placebo | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -5.9 µg/dL | Standard Deviation 17.96 |
| Placebo | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -9.9 µg/dL | Standard Deviation 25.7 |
| Placebo | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 243.1 µg/dL | Standard Deviation 40.02 |
| Placebo | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 4.1 µg/dL | Standard Deviation 23.83 |
| Placebo | Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -5.5 µg/dL | Standard Deviation 22.51 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.02942 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00212 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00042 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.09252 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.04332 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00042 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00052 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.16262 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.03662 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00122 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.17792 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.58672 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.13062 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.98892 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.20262 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.57032 sided t-test/Wilcoxon Signed-rank Test
Secondary
Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Unsaturated Iron Binding Capacity was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 15.3 µg/dL | Standard Deviation 30.52 |
| AKB-6548 240 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 14.4 µg/dL | Standard Deviation 25.96 |
| AKB-6548 240 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 153.4 µg/dL | Standard Deviation 34.26 |
| AKB-6548 240 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 15.1 µg/dL | Standard Deviation 30.46 |
| AKB-6548 240 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 10.9 µg/dL | Standard Deviation 18.78 |
| AKB-6548 370 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 34.0 µg/dL | Standard Deviation 25.62 |
| AKB-6548 370 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 26.1 µg/dL | Standard Deviation 22.3 |
| AKB-6548 370 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 22.4 µg/dL | Standard Deviation 19.52 |
| AKB-6548 370 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 16.2 µg/dL | Standard Deviation 22.74 |
| AKB-6548 370 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 168.0 µg/dL | Standard Deviation 52.46 |
| AKB-6548 500 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 31.5 µg/dL | Standard Deviation 27.08 |
| AKB-6548 500 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 173.1 µg/dL | Standard Deviation 56.48 |
| AKB-6548 500 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 17.2 µg/dL | Standard Deviation 32.16 |
| AKB-6548 500 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 29.3 µg/dL | Standard Deviation 16.06 |
| AKB-6548 500 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | -0.7 µg/dL | Standard Deviation 23.06 |
| AKB-6548 630 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 3.9 µg/dL | Standard Deviation 42.2 |
| AKB-6548 630 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 171.2 µg/dL | Standard Deviation 38.77 |
| AKB-6548 630 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | 49.6 µg/dL | Standard Deviation 26.5 |
| AKB-6548 630 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | 37.4 µg/dL | Standard Deviation 20.16 |
| AKB-6548 630 mg | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | 21.3 µg/dL | Standard Deviation 27.4 |
| Placebo | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 4 | -3.7 µg/dL | Standard Deviation 27.89 |
| Placebo | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 6 | -1.3 µg/dL | Standard Deviation 17.81 |
| Placebo | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Baseline | 175.5 µg/dL | Standard Deviation 33.14 |
| Placebo | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Follow-up Visit (up to Week 8) | 0.7 µg/dL | Standard Deviation 20.72 |
| Placebo | Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8) | Change from Baseline to Week 2 | -1.5 µg/dL | Standard Deviation 20.61 |
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.04482 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00042 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.08132 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.00382 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 2).p-value: =0.68612 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.05532 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.00042 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 4).p-value: =0.73792 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.0722 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Week 6).p-value: =0.67812 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.05242 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.03672 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.66712 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.68612 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group (Change from Baseline to Follow-up).p-value: =0.90122 sided t-test/Wilcoxon Signed-rank Test
Secondary
Maximum Change From Baseline in HCT
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that HCT concentration increased.
Time frame: Baseline; up to Week 8
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Maximum Change From Baseline in HCT | Baseline | 29.0 Percentage of red blood cells | Standard Deviation 2.57 |
| AKB-6548 240 mg | Maximum Change From Baseline in HCT | Maximum change from Baseline (up to Week 8) | 2.94 Percentage of red blood cells | Standard Deviation 2.578 |
| AKB-6548 370 mg | Maximum Change From Baseline in HCT | Baseline | 29.6 Percentage of red blood cells | Standard Deviation 2.45 |
| AKB-6548 370 mg | Maximum Change From Baseline in HCT | Maximum change from Baseline (up to Week 8) | 2.56 Percentage of red blood cells | Standard Deviation 2.097 |
| AKB-6548 500 mg | Maximum Change From Baseline in HCT | Baseline | 30.4 Percentage of red blood cells | Standard Deviation 2.41 |
| AKB-6548 500 mg | Maximum Change From Baseline in HCT | Maximum change from Baseline (up to Week 8) | 4.43 Percentage of red blood cells | Standard Deviation 2.277 |
| AKB-6548 630 mg | Maximum Change From Baseline in HCT | Maximum change from Baseline (up to Week 8) | 4.84 Percentage of red blood cells | Standard Deviation 3.452 |
| AKB-6548 630 mg | Maximum Change From Baseline in HCT | Baseline | 29.6 Percentage of red blood cells | Standard Deviation 3.68 |
| Placebo | Maximum Change From Baseline in HCT | Baseline | 29.8 Percentage of red blood cells | Standard Deviation 1.96 |
| Placebo | Maximum Change From Baseline in HCT | Maximum change from Baseline (up to Week 8) | 1.89 Percentage of red blood cells | Standard Deviation 1.729 |
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00042 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Secondary
Maximum Change From Baseline in Hgb
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased.
Time frame: Baseline; up to Week 8
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Maximum Change From Baseline in Hgb | Baseline | 9.46 g/dL | Standard Deviation 0.792 |
| AKB-6548 240 mg | Maximum Change From Baseline in Hgb | Maximum change from Baseline (up to Week 8) | 1.04 g/dL | Standard Deviation 0.585 |
| AKB-6548 370 mg | Maximum Change From Baseline in Hgb | Baseline | 9.93 g/dL | Standard Deviation 0.643 |
| AKB-6548 370 mg | Maximum Change From Baseline in Hgb | Maximum change from Baseline (up to Week 8) | 0.82 g/dL | Standard Deviation 0.581 |
| AKB-6548 500 mg | Maximum Change From Baseline in Hgb | Baseline | 9.86 g/dL | Standard Deviation 0.606 |
| AKB-6548 500 mg | Maximum Change From Baseline in Hgb | Maximum change from Baseline (up to Week 8) | 1.44 g/dL | Standard Deviation 0.675 |
| AKB-6548 630 mg | Maximum Change From Baseline in Hgb | Maximum change from Baseline (up to Week 8) | 1.54 g/dL | Standard Deviation 0.911 |
| AKB-6548 630 mg | Maximum Change From Baseline in Hgb | Baseline | 9.67 g/dL | Standard Deviation 0.796 |
| Placebo | Maximum Change From Baseline in Hgb | Baseline | 9.83 g/dL | Standard Deviation 0.677 |
| Placebo | Maximum Change From Baseline in Hgb | Maximum change from Baseline (up to Week 8) | 0.59 g/dL | Standard Deviation 0.568 |
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00022 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Secondary
Maximum Change From Baseline in RBC Count
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that RBC count increased.
Time frame: Baseline; up to Week 8
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Maximum Change From Baseline in RBC Count | Baseline | 3.21 10^6 cells/μL | Standard Deviation 0.415 |
| AKB-6548 240 mg | Maximum Change From Baseline in RBC Count | Maximum change from Baseline (up to Week 8) | 0.31 10^6 cells/μL | Standard Deviation 0.21 |
| AKB-6548 370 mg | Maximum Change From Baseline in RBC Count | Baseline | 3.38 10^6 cells/μL | Standard Deviation 0.286 |
| AKB-6548 370 mg | Maximum Change From Baseline in RBC Count | Maximum change from Baseline (up to Week 8) | 0.22 10^6 cells/μL | Standard Deviation 0.239 |
| AKB-6548 500 mg | Maximum Change From Baseline in RBC Count | Baseline | 3.37 10^6 cells/μL | Standard Deviation 0.286 |
| AKB-6548 500 mg | Maximum Change From Baseline in RBC Count | Maximum change from Baseline (up to Week 8) | 0.44 10^6 cells/μL | Standard Deviation 0.249 |
| AKB-6548 630 mg | Maximum Change From Baseline in RBC Count | Maximum change from Baseline (up to Week 8) | 0.44 10^6 cells/μL | Standard Deviation 0.291 |
| AKB-6548 630 mg | Maximum Change From Baseline in RBC Count | Baseline | 3.25 10^6 cells/μL | Standard Deviation 0.366 |
| Placebo | Maximum Change From Baseline in RBC Count | Baseline | 3.34 10^6 cells/μL | Standard Deviation 0.463 |
| Placebo | Maximum Change From Baseline in RBC Count | Maximum change from Baseline (up to Week 8) | 0.18 10^6 cells/μL | Standard Deviation 0.183 |
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00432 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00012 sided t-test/Wilcoxon Signed-rank Test
Secondary
Maximum Change in Absolute Reticulocyte Count From Baseline
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline absolute reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that reticulocyte count increased.
Time frame: Baseline; up to Week 8
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Baseline | 0.0766 10^6 cells/μL | Standard Deviation 0.02855 |
| AKB-6548 240 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Maximum Change from Baseline (up to Week 8) | 0.013 10^6 cells/μL | Standard Deviation 0.0145 |
| AKB-6548 370 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Baseline | 0.0569 10^6 cells/μL | Standard Deviation 0.01891 |
| AKB-6548 370 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Maximum Change from Baseline (up to Week 8) | 0.028 10^6 cells/μL | Standard Deviation 0.0184 |
| AKB-6548 500 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Baseline | 0.0811 10^6 cells/μL | Standard Deviation 0.01993 |
| AKB-6548 500 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Maximum Change from Baseline (up to Week 8) | 0.040 10^6 cells/μL | Standard Deviation 0.02 |
| AKB-6548 630 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Maximum Change from Baseline (up to Week 8) | 0.042 10^6 cells/μL | Standard Deviation 0.0263 |
| AKB-6548 630 mg | Maximum Change in Absolute Reticulocyte Count From Baseline | Baseline | 0.0674 10^6 cells/μL | Standard Deviation 0.02715 |
| Placebo | Maximum Change in Absolute Reticulocyte Count From Baseline | Baseline | 0.0700 10^6 cells/μL | Standard Deviation 0.03319 |
| Placebo | Maximum Change in Absolute Reticulocyte Count From Baseline | Maximum Change from Baseline (up to Week 8) | 0.011 10^6 cells/μL | Standard Deviation 0.0129 |
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00272 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: <0.00012 sided t-test/Wilcoxon Signed-rank Test
Comparison: p-value was based on the comparison within treatment group.p-value: =0.00052 sided t-test/Wilcoxon Signed-rank Test
Secondary
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected).
Time frame: Baseline, Week 6
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QTC Interval | 424.9 Milliseconds | Standard Deviation 27.7 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QTC Interval | 5.1 Milliseconds | Standard Deviation 14.33 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QRS Duration | 94.9 Milliseconds | Standard Deviation 21.35 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QRS Duration | 4.1 Milliseconds | Standard Deviation 9.52 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QT Interval | 412.0 Milliseconds | Standard Deviation 41.59 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline PR Interval | 156.7 Milliseconds | Standard Deviation 46.9 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QT Interval | 3.8 Milliseconds | Standard Deviation 24.78 |
| AKB-6548 240 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline PR Interval | -0.8 Milliseconds | Standard Deviation 22.95 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QT Interval | 7.8 Milliseconds | Standard Deviation 25.33 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QRS Duration | 2.0 Milliseconds | Standard Deviation 13.29 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QTC Interval | 436.3 Milliseconds | Standard Deviation 37.56 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QT Interval | 421.4 Milliseconds | Standard Deviation 46.58 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QRS Duration | 113.8 Milliseconds | Standard Deviation 37.57 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QTC Interval | 3.6 Milliseconds | Standard Deviation 17.65 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline PR Interval | 2.2 Milliseconds | Standard Deviation 12.37 |
| AKB-6548 370 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline PR Interval | 174.6 Milliseconds | Standard Deviation 40.89 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline PR Interval | 11.4 Milliseconds | Standard Deviation 29.72 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QRS Duration | 97.1 Milliseconds | Standard Deviation 28.07 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline PR Interval | 172.8 Milliseconds | Standard Deviation 51.06 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QRS Duration | -1.3 Milliseconds | Standard Deviation 7.23 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QT Interval | -1.6 Milliseconds | Standard Deviation 19.83 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QT Interval | 419.0 Milliseconds | Standard Deviation 44.97 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QTC Interval | 445.1 Milliseconds | Standard Deviation 36.1 |
| AKB-6548 500 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QTC Interval | -5.8 Milliseconds | Standard Deviation 20.7 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QT Interval | 406.9 Milliseconds | Standard Deviation 42.97 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QTC Interval | -1.6 Milliseconds | Standard Deviation 16.74 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QTC Interval | 427.6 Milliseconds | Standard Deviation 23.6 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QRS Duration | 94.5 Milliseconds | Standard Deviation 12.65 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline PR Interval | 187.8 Milliseconds | Standard Deviation 45.72 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QT Interval | 4.5 Milliseconds | Standard Deviation 24.1 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QRS Duration | 1.4 Milliseconds | Standard Deviation 10.28 |
| AKB-6548 630 mg | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline PR Interval | -11.7 Milliseconds | Standard Deviation 63.75 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QTC Interval | 3.3 Milliseconds | Standard Deviation 21.46 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline PR Interval | 175.8 Milliseconds | Standard Deviation 31.82 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline PR Interval | -0.4 Milliseconds | Standard Deviation 13.07 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QRS Duration | 94.6 Milliseconds | Standard Deviation 12.52 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QRS Duration | -1.6 Milliseconds | Standard Deviation 5.33 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QT Interval | 419.1 Milliseconds | Standard Deviation 40.1 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Change from Baseline QT Interval | 11.0 Milliseconds | Standard Deviation 23.35 |
| Placebo | Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval | Baseline QTC Interval | 435.6 Milliseconds | Standard Deviation 17.9 |
Secondary
Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4
Plasma samples were collected for the analysis.
Time frame: Week 2: Pre-dose; Week 4: Pre-dose
Population: PK population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 1999.3 μg/mL | Standard Deviation 1427.74 |
| AKB-6548 240 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 1848.4 μg/mL | Standard Deviation 979.73 |
| AKB-6548 370 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 2687.5 μg/mL | Standard Deviation 2027.63 |
| AKB-6548 370 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 2708.5 μg/mL | Standard Deviation 1879.02 |
| AKB-6548 500 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 5900.1 μg/mL | Standard Deviation 8309.24 |
| AKB-6548 500 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 6866.9 μg/mL | Standard Deviation 9247.39 |
| AKB-6548 630 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 6425.0 μg/mL | Standard Deviation 7214.67 |
| AKB-6548 630 mg | Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 7960.8 μg/mL | Standard Deviation 6643.98 |
Secondary
Mean Plasma Vadadustat Concentrations on Week 2 and Week 4
Plasma samples were collected for the analysis.
Time frame: Week 2: Pre-dose and post-dose; Week 4: Pre-dose
Population: Pharmacokinetic (PK) Population: All participants in the ITT population that had pre-dose PK sampling that fell within a range of 18 to 30 hours after the previous dose of study medication or post-dose PK sampling that fell in a range of 2 to 8 hours post-dose. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKB-6548 240 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 4358.28 μg/mL | Standard Deviation 2549.623 |
| AKB-6548 240 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 4698.21 μg/mL | Standard Deviation 3520.52 |
| AKB-6548 240 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Post-Dose | 17036.82 μg/mL | Standard Deviation 8035.308 |
| AKB-6548 370 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 6640.04 μg/mL | Standard Deviation 5141.484 |
| AKB-6548 370 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 7884.56 μg/mL | Standard Deviation 5517.132 |
| AKB-6548 370 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Post-Dose | 21371.63 μg/mL | Standard Deviation 8664.304 |
| AKB-6548 500 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Post-Dose | 39892.00 μg/mL | Standard Deviation 19891.284 |
| AKB-6548 500 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 10791.79 μg/mL | Standard Deviation 9823.143 |
| AKB-6548 500 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 14274.80 μg/mL | Standard Deviation 16141.439 |
| AKB-6548 630 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Pre-Dose | 12443.17 μg/mL | Standard Deviation 17095.495 |
| AKB-6548 630 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 4 Pre-Dose | 17700.17 μg/mL | Standard Deviation 19532.648 |
| AKB-6548 630 mg | Mean Plasma Vadadustat Concentrations on Week 2 and Week 4 | Week 2 Post-Dose | 41656.11 μg/mL | Standard Deviation 20002.713 |
Secondary
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. A TEAE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. A SAE included AEs that met one or more of the following criteria/outcomes: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.
Time frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Population: ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKB-6548 240 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 9 Participants |
| AKB-6548 240 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| AKB-6548 370 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 6 Participants |
| AKB-6548 370 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
| AKB-6548 500 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| AKB-6548 500 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| AKB-6548 630 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| AKB-6548 630 mg | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| Placebo | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| Placebo | Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
Secondary
Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Up to Week 6 (End of the Dosing Period)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKB-6548 240 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.4 g/dL | 3 Participants |
| AKB-6548 240 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.6 g/dL | 3 Participants |
| AKB-6548 240 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.8 g/dL | 3 Participants |
| AKB-6548 240 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥1.0 g/dL | 5 Participants |
| AKB-6548 370 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.4 g/dL | 2 Participants |
| AKB-6548 370 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥1.0 g/dL | 6 Participants |
| AKB-6548 370 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.6 g/dL | 2 Participants |
| AKB-6548 370 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.8 g/dL | 2 Participants |
| AKB-6548 500 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥1.0 g/dL | 11 Participants |
| AKB-6548 500 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.6 g/dL | 0 Participants |
| AKB-6548 500 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.8 g/dL | 3 Participants |
| AKB-6548 500 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.4 g/dL | 2 Participants |
| AKB-6548 630 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.4 g/dL | 1 Participants |
| AKB-6548 630 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.6 g/dL | 1 Participants |
| AKB-6548 630 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥1.0 g/dL | 14 Participants |
| AKB-6548 630 mg | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.8 g/dL | 1 Participants |
| Placebo | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥1.0 g/dL | 2 Participants |
| Placebo | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.8 g/dL | 0 Participants |
| Placebo | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.6 g/dL | 0 Participants |
| Placebo | Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period | Change from Baseline in Hgb ≥0.4 g/dL | 2 Participants |
Secondary
Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Up to Week 6 (End of The Dosing Period)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKB-6548 240 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥5% | 4 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥10.0% | 4 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥7.5% | 1 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥7.5% | 0 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥5% | 3 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥10.0% | 6 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥7.5% | 0 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥5% | 2 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥10.0% | 9 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥5% | 0 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥10.0% | 11 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥7.5% | 4 Participants |
| Placebo | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥7.5% | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥5% | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in HCT ≥10.0% | 1 Participants |
Secondary
Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Up to Week 6 (End of The Dosing Period)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKB-6548 240 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥5% | 4 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥10.0% | 5 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥7.5% | 4 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥7.5% | 3 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥5% | 3 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥10.0% | 5 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥7.5% | 3 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥5% | 1 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥10.0% | 11 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥5% | 1 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥10.0% | 14 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥7.5% | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥7.5% | 0 Participants |
| Placebo | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥5% | 2 Participants |
| Placebo | Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in Hgb ≥10.0% | 2 Participants |
Secondary
Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Up to Week 6 (End of The Dosing Period)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKB-6548 240 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥5% | 4 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥10.0% | 2 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥7.5% | 2 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥7.5% | 2 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥5% | 3 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥10.0% | 4 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥7.5% | 3 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥5% | 2 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥10.0% | 8 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥5% | 3 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥10.0% | 11 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥7.5% | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥7.5% | 0 Participants |
| Placebo | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥5% | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period | % Change from Baseline in RBCs ≥10.0% | 1 Participants |
Secondary
Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period
Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline reticulocytes count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline.
Time frame: Up to Week 6 (End of The Dosing Period)
Population: MITT population. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKB-6548 240 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥6000 cells/uL | 1 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥18000 cells/uL | 2 Participants |
| AKB-6548 240 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥12000 cells/uL | 1 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥12000 cells/uL | 3 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥6000 cells/uL | 1 Participants |
| AKB-6548 370 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥18000 cells/uL | 5 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥12000 cells/uL | 0 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥6000 cells/uL | 4 Participants |
| AKB-6548 500 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥18000 cells/uL | 4 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥6000 cells/uL | 2 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥18000 cells/uL | 5 Participants |
| AKB-6548 630 mg | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥12000 cells/uL | 3 Participants |
| Placebo | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥12000 cells/uL | 1 Participants |
| Placebo | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥6000 cells/uL | 3 Participants |
| Placebo | Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period | Change from Baseline in Reticulocytes ≥18000 cells/uL | 2 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. Clinical significance is determined by the investigator. The investigator was responsible for reviewing laboratory results for clinical significance.
Time frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Population: ITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKB-6548 240 mg | Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings | 0 Participants |
| AKB-6548 370 mg | Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings | 0 Participants |
| AKB-6548 500 mg | Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings | 0 Participants |
| AKB-6548 630 mg | Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology, serum chemistry, C-reactive protein, DHEA-S, VEGF, and cystatin C. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Population: ITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKB-6548 240 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| AKB-6548 370 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| AKB-6548 500 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| AKB-6548 630 mg | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter
Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Population: ITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKB-6548 240 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter | 0 Participants |
| AKB-6548 370 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter | 0 Participants |
| AKB-6548 500 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter | 0 Participants |
| AKB-6548 630 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter | 0 Participants |