Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of trelagliptin when administered at a dose of 25 mg once weekly using placebo as a control in patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one antidiabetic drug in addition to diet and/or exercise therapy (if given); and to evaluate the long-term efficacy and safety of trelagliptin when administered at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease.
Detailed description
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, comparative study (Treatment Period I) and a phase 3, multicenter, open-label, long-term study (Treatment Period II) to evaluate the efficacy and safety of trelagliptin when administered orally at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one antidiabetic drug in addition to diet and/or exercise therapy (if given).
Interventions
DRUGTrelagliptin 25 mg
Trelagliptin 25 mg Tablets
DRUGPlacebo
Placebo Tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The participant has a diagnosis of type 2 diabetes mellitus. 2. The participant has a fasting C-peptide value of 0.6 ng/mL or higher at the start of the screening period (Week -6) and Week -2 of the screening period. 3. The participant has a hemoglobin value of 10.0 g/dL or higher at the start of the screening period (Week -6) and Week -2 of the screening period. 4. The participant has a Haemoglobin A1c (HbA1c) value of 7.0% or higher but less than 10.0% at Week -2 of the screening period. For participants undergoing hemodialysis (with End-stage Renal Disease \[ESRD\]), those with a glycoalbumin value of 20% or higher could be enrolled even if their HbA1c value is below 7.0% at Week -2 of the screening period. 5. \<HbA1c value of 7.0% or higher but less than 10.0% at Week -2 of the screening period\> The participant has an HbA1c value difference between the start of the screening period (Week -6) and Week -2 of the screening period within 10.0%\* of the HbA1c value at the start of the screening period (Week -6). \<For participants undergoing hemodialysis (with ESRD), glycoalbumin value of 20% or higher and HbA1c value of below 7.0% at Week -2 of the screening period\> The participant has a glycoalbumin difference between the start of the screening period (Week -6) and Week -2 of the screening period within 10.0%\* of the glycoalbumin value at the start of the screening period (Week -6). \*: rounded to one decimal place 6. The participant has been on a fixed diet and/or exercise therapy (if any) for at least 6 weeks prior to the start of the screening period (Week -6). 7. The participant meets any of the following: * The participant has not received any antidiabetic medications (including insulin preparations) from at least 6 weeks prior to the start of the screening period (Week -6). * The participant is being treated with one oral hypoglycemic drug\* starting from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen. \*: any one of the following medications: mitiglinide calcium hydrate, repaglinide, acarbose, miglitol, or voglibose * The participant is being treated with one insulin preparation\*\* starting from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen (≤40 units/day) of the insulin preparation. * Any one of the following insulin monotherapies: mixed (short-acting or rapid-acting insulin containing no more than 30% volume), intermediate-acting, or long-acting soluble insulin preparations 8. The participant is not undergoing hemodialysis or peritoneal dialysis and has severe renal impairment \[creatinine clearance (Ccr) \<30 mL/min at the start of the screening period (Week -6)\], or the participant is undergoing hemodialysis and has end-stage renal failure. 9. In the opinion of the investigator or sub-investigator, the initiation of hemodialysis or peritoneal dialysis at least within 12 weeks after starting the investigational product is not expected. \[in cases where the participant is not undergoing hemodialysis or peritoneal dialysis (patients with severe renal impairment)\] 10. The participant has been undergoing hemodialysis starting from at least 6 months prior to informed consent and, in the opinion of the investigator or sub-investigator, the participant is clinically stable. \[in cases where the participant is undergoing hemodialysis (patient with end-stage renal failure)\] 11. The participant is male or female and is aged 20 years or older at the time of informed consent. 12. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent until one month after the end of the study. 13. In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements. 14. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
Exclusion criteria
1. The participant has clinically evident hepatic impairment \[e.g., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 times the upper limit of normal or total bilirubin of ≥2.0 mg/dL at the start of the screening period (Week -6) or at Week -2 of the screening period\]. 2. The participant has any serious cardiac diseases, cerebrovascular disorders, or serious pancreatic or hematological diseases (e.g., participants who require inpatient treatment or are hospitalized for treatment within 24 weeks prior to the start of the screening period). 3. The participant has severe ketosis, diabetic coma or precoma, type 1 diabetes, severe infection, before or after surgery, or severe external trauma. 4. The participant has hemoglobinopathy (sickle cell disease, thalassemia, etc.). 5. The participant experienced hypoglycemia (participants with a blood glucose value of ≤70 mg/dL or hypoglycemic symptoms) within 6 weeks prior to the start of the screening period or during the screening period (at least twice per week). 6. The participant has inadequately controlled hypertension. 7. For participants who are being treated with one antidiabetic agent, the participant was using at least two antidiabetic therapies on the day before 6 weeks prior to the start of the screening period (Week -6) (43 days prior to the start of the screening period). 8. The participant has malignancies. 9. The participant has a history of hypersensitivity or allergies to dipeptidyl peptidase 4 (DPP-4) inhibitors. 10. The participant has a history of gastrectomy or small intestinal resection. 11. The participant is a habitual drinker and consumes a daily average of more than 100 mL of alcohol. 12. The participant has a history of drug abuse (defined as the use of an illegal drug) or alcohol dependence. 13. The participant is required to take excluded medications during the study period. 14. The participant has previously received trelagliptin. 15. The participant received any other investigational products (including study drugs in a post-marketing clinical study) within 12 weeks prior to the start of the screening period. 16. The participant is participating in other clinical studies at the time of informed consent. 17. If female, the participant is pregnant or lactating or intending to become pregnant from the time of informed consent to within 1 month after the end of the study; or intending to donate ova during such time period. 18. The participant is an immediate family member of a study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. 19. The participant is hospitalized during the screening period or is deemed as requiring hospitalization during the study period by the investigator or sub-investigator, unless the hospitalization is for short-term evaluations including complete health checkups or shunt (including shunt maintenance). 20. The participant is deemed ineligible for the study for any other reason by the investigator or sub-investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at the End of Treatment Period I | Baseline (Week 0) and end of Treatment Period I (Up to Week 12) | — |
| Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE) Before the Start of Study Drug Administration in Treatment Period II | Up to Week 12 | An Adverse Event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a drug (including the study drug). It does not necessarily have to have a causal relationship with this treatment (including the study drug). An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug (including the study drug), whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Reported data is the number of participants reporting one or more TEAEs that occurred before the start of Treatment Period II in each group. |
| Number of Participants Who Had One or More TEAE Occurred After 1st Dose of Trelagliptin 25 mg Tablet | Up to Week 54 | An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a drug (including the study drug). It does not necessarily have to have a causal relationship with this treatment (including the study drug). An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug (including the study drug), whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. As to collect the safety data of long-term treatment with the active drug widely, the number of participants reporting one or more TEAEs that occurred after 1st dose of trelagliptin 25 mg, that is events in Period I and II for Trelagliptin 25 mg group and events in Period II for Placebo and Trelagliptin 25 mg group, was analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycoalbumin | Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52) | Reported data was the change from baseline in glycoalbumin at each time point. |
| Numbers of Participants With TEAE Related to Vital Signs Before the Start of Study Drug Administration in Treatment Period II | Up to Week 12 | Number of participants with a vital sign-related TEAE classified under the System Organ Class of investigations, was reported. |
| Changes From Baseline in HbA1c | Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52) | Reported data was the change from baseline in HbA1c at each time point. |
| Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II | Up to Week 12 | Here U/L is Unit/Litter, and ULN is Upper Limit of Normal. |
| Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | Up to Week 12 | Here QTcF is corrected QT interval by Fridericia formula. |
| Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | At the end of Treatment Period I (Up to Week 12) and Period II (Up to Week 52) | — |
| Change From Baseline in Fasting Plasma Glucose | Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52) | Reported data was the change from baseline in fasting plasma glucose at each time point. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 41 investigative sites in Japan, from 7 August 2015 to 24 April 2018.
Pre-assignment details
Participants with a historical diagnosis of type 2 diabetes mellitus complicated by severe renal impairment or end stage renal disease (ESRD) were enrolled in one of the two treatment groups: trelagliptin 25 milligram (mg) throughout Period I and II, Placebo in Period I followed by trelagliptin 25 mg in Period II.
Participants by arm
| Arm | Count |
|---|---|
| Trelagliptin 25 mg Trelagliptin 25 mg tablet, orally, once weekly before breakfast for up to Week 52 (Period I + II) | 55 |
| Placebo and Trelagliptin 25 mg Placebo tablet, orally, once weekly before breakfast for up to Week 12 (Period I), followed by trelagliptin 25 mg tablet, orally, once weekly before breakfast for up to Week 52 (Period II) | 52 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Major Protocol Deviation | 1 | 0 |
| Overall Study | Pretreatment Event/Adverse Event | 8 | 6 |
| Overall Study | Reason Not Specified | 3 | 5 |
| Overall Study | Voluntary Withdrawal | 0 | 1 |
Baseline characteristics
| Characteristic | Trelagliptin 25 mg | Placebo and Trelagliptin 25 mg | Total |
|---|---|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 10.28 | 65.8 Years STANDARD_DEVIATION 10.46 | 65.8 Years STANDARD_DEVIATION 10.32 |
| Antidiabetic Drug at the start of the screening period (Week -6) No | 20 Participants | 19 Participants | 39 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6) Yes | 35 Participants | 33 Participants | 68 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Acarbose | 0 Participants | 2 Participants | 2 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Insulin Preparation No | 37 Participants | 39 Participants | 76 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Insulin Preparation Yes | 18 Participants | 13 Participants | 31 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Miglitol | 3 Participants | 2 Participants | 5 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Mitiglinide Calcium Hydrate | 5 Participants | 3 Participants | 8 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Rapid-acting Insulin Secretagogue No | 46 Participants | 44 Participants | 90 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Rapid-acting Insulin Secretagogue Yes | 9 Participants | 8 Participants | 17 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Repaglinide | 4 Participants | 5 Participants | 9 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Type of Insulin Preparation Long-Acting | 9 Participants | 7 Participants | 16 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Type of Insulin Preparation Pre-Mixed | 8 Participants | 5 Participants | 13 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): Voglibose | 5 Participants | 8 Participants | 13 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): α-Glucosidase Inhibitor No | 47 Participants | 40 Participants | 87 Participants |
| Antidiabetic Drug at the start of the screening period (Week -6): α-Glucosidase Inhibitor Yes | 8 Participants | 12 Participants | 20 Participants |
| BMI | 24.41 Kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 3.525 | 24.97 Kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 4.017 | 24.68 Kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 3.765 |
| Creatinine Clearance | 10.7 Milliliter (mL)/ minute (min) STANDARD_DEVIATION 8.32 | 11.3 Milliliter (mL)/ minute (min) STANDARD_DEVIATION 8.29 | 11.0 Milliliter (mL)/ minute (min) STANDARD_DEVIATION 8.27 |
| Dipeptidyl-Peptidase-4 (DPP-4) Activity | 8.4745 Nanomole(nmol)/min/mL STANDARD_DEVIATION 1.98793 | 8.4200 Nanomole(nmol)/min/mL STANDARD_DEVIATION 2.04675 | 8.4478 Nanomole(nmol)/min/mL STANDARD_DEVIATION 2.00754 |
| Duration of Diabetes | 239.7 Months STANDARD_DEVIATION 116.8 | 219.3 Months STANDARD_DEVIATION 106.35 | 229.8 Months STANDARD_DEVIATION 111.79 |
| Estimated Glomerular Filtration Rate (eGFR) | 8.3 mL/min/1.73 m^2 STANDARD_DEVIATION 7.28 | 8.7 mL/min/1.73 m^2 STANDARD_DEVIATION 8 | 8.5 mL/min/1.73 m^2 STANDARD_DEVIATION 7.61 |
| Exercise Program No | 42 Participants | 40 Participants | 82 Participants |
| Exercise Program Yes | 13 Participants | 12 Participants | 25 Participants |
| Fasting C-Peptide | 7.07 Nanogram (ng)/mL STANDARD_DEVIATION 5.481 | 7.41 Nanogram (ng)/mL STANDARD_DEVIATION 4.58 | 7.23 Nanogram (ng)/mL STANDARD_DEVIATION 5.042 |
| Fasting Glucagon | 177.4 Picogram (pg)/mL STANDARD_DEVIATION 55.4 | 165.7 Picogram (pg)/mL STANDARD_DEVIATION 38.13 | 171.7 Picogram (pg)/mL STANDARD_DEVIATION 47.93 |
| Fasting Plasma Glucose | 143.1 Milligram (mg)/deciliter (dL) STANDARD_DEVIATION 32.58 | 151.1 Milligram (mg)/deciliter (dL) STANDARD_DEVIATION 39.3 | 147.0 Milligram (mg)/deciliter (dL) STANDARD_DEVIATION 36.05 |
| Glycoalbumin | 23.21 Percent STANDARD_DEVIATION 4.091 | 24.29 Percent STANDARD_DEVIATION 4.565 | 23.74 Percent STANDARD_DEVIATION 4.341 |
| Hemoglobin A1c (HbA1c) | 7.57 Percent STANDARD_DEVIATION 0.849 | 7.74 Percent STANDARD_DEVIATION 1.049 | 7.65 Percent STANDARD_DEVIATION 0.951 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Japan | 55 Participants | 52 Participants | 107 Participants |
| Sex: Female, Male Female | 17 Participants | 13 Participants | 30 Participants |
| Sex: Female, Male Male | 38 Participants | 39 Participants | 77 Participants |
| Undergoing Hemodialysis No (Severe Renal Impairment) | 15 Participants | 13 Participants | 28 Participants |
| Undergoing Hemodialysis Yes (End Stage Renal Disease) | 40 Participants | 39 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 48 |
| other Total, other adverse events | 48 / 55 | 39 / 48 |
| serious Total, serious adverse events | 23 / 55 | 16 / 48 |
Outcome results
Primary
Change From Baseline in HbA1c at the End of Treatment Period I
Time frame: Baseline (Week 0) and end of Treatment Period I (Up to Week 12)
Population: Full Analysis Set: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Trelagliptin 25 mg | Change From Baseline in HbA1c at the End of Treatment Period I | -0.71 Percent HbA1c | Standard Error 0.087 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in HbA1c at the End of Treatment Period I | 0.01 Percent HbA1c | Standard Error 0.089 |
p-value: <0.000195% CI: [-0.966, -0.473]ANCOVA
Primary
Number of Participants Who Had One or More TEAE Occurred After 1st Dose of Trelagliptin 25 mg Tablet
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a drug (including the study drug). It does not necessarily have to have a causal relationship with this treatment (including the study drug). An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug (including the study drug), whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. As to collect the safety data of long-term treatment with the active drug widely, the number of participants reporting one or more TEAEs that occurred after 1st dose of trelagliptin 25 mg, that is events in Period I and II for Trelagliptin 25 mg group and events in Period II for Placebo and Trelagliptin 25 mg group, was analyzed.
Time frame: Up to Week 54
Population: Safety Analysis Set: The safety analysis set was defined as all participants who received at least one dose of the study drug. Number analyzed is the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trelagliptin 25 mg | Number of Participants Who Had One or More TEAE Occurred After 1st Dose of Trelagliptin 25 mg Tablet | 54 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Who Had One or More TEAE Occurred After 1st Dose of Trelagliptin 25 mg Tablet | 48 Participants |
Primary
Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE) Before the Start of Study Drug Administration in Treatment Period II
An Adverse Event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a drug (including the study drug). It does not necessarily have to have a causal relationship with this treatment (including the study drug). An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug (including the study drug), whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Reported data is the number of participants reporting one or more TEAEs that occurred before the start of Treatment Period II in each group.
Time frame: Up to Week 12
Population: Safety Analysis Set: The safety analysis set was defined as all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trelagliptin 25 mg | Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE) Before the Start of Study Drug Administration in Treatment Period II | 40 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE) Before the Start of Study Drug Administration in Treatment Period II | 32 Participants |
Secondary
Change From Baseline in Fasting Plasma Glucose
Reported data was the change from baseline in fasting plasma glucose at each time point.
Time frame: Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)
Population: Full Analysis Set: All randomized participants who received at least one dose of study drug. The analyzed numbers for each arm were participants who were evaluable for this outcome measure at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At the End of Treatment Period II | -14.3 mg/dL | Standard Deviation 37.48 |
| Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 2 | -12.9 mg/dL | Standard Deviation 22.67 |
| Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 4 | -11.3 mg/dL | Standard Deviation 31.25 |
| Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 8 | -12.7 mg/dL | Standard Deviation 25.56 |
| Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 12 | -15.9 mg/dL | Standard Deviation 31.95 |
| Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At the End of Treatment Period I | -14.8 mg/dL | Standard Deviation 31.51 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 12 | -0.3 mg/dL | Standard Deviation 24.86 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At the End of Treatment Period II | -7.3 mg/dL | Standard Deviation 34.31 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 8 | -4.3 mg/dL | Standard Deviation 27.28 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 2 | 2.3 mg/dL | Standard Deviation 20.78 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At the End of Treatment Period I | 0.8 mg/dL | Standard Deviation 25.5 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | At Week 4 | -2.6 mg/dL | Standard Deviation 32.49 |
Comparison: Change from baseline in fasting plasma glucose at Week 2 was compared between the treatment groups.95% CI: [-23.59, -6.88]
Comparison: Change from baseline in fasting plasma glucose at Week 4 was compared between the treatment groups.95% CI: [-20.98, 3.58]
Comparison: Change from baseline in fasting plasma glucose at Week 8 was compared between the treatment groups.95% CI: [-18.76, 2.11]
Comparison: Change from baseline in fasting plasma glucose at Week 12 was compared between the treatment groups.95% CI: [-27.14, -4.03]
Comparison: Change from baseline in fasting plasma glucose at End of Treatment Period I was compared between the treatment groups.95% CI: [-26.67, -4.62]
Secondary
Change From Baseline in Glycoalbumin
Reported data was the change from baseline in glycoalbumin at each time point.
Time frame: Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)
Population: Full Analysis Set: All randomized participants who received at least one dose of study drug. The analyzed numbers for each arm were participants who were evaluable for this outcome measure at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 2 | -1.67 Percent | Standard Deviation 1.137 |
| Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 4 | -2.46 Percent | Standard Deviation 1.534 |
| Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 8 | -2.69 Percent | Standard Deviation 2.038 |
| Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 12 | -2.85 Percent | Standard Deviation 2.523 |
| Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At the End of Treatment Period I | -2.81 Percent | Standard Deviation 2.401 |
| Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At the End of Treatment Period II | -3.12 Percent | Standard Deviation 2.58 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At the End of Treatment Period I | -0.15 Percent | Standard Deviation 2.537 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 2 | 0.10 Percent | Standard Deviation 1.059 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 12 | -0.27 Percent | Standard Deviation 2.563 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 4 | -0.01 Percent | Standard Deviation 1.474 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At the End of Treatment Period II | -3.06 Percent | Standard Deviation 2.604 |
| Placebo and Trelagliptin 25 mg | Change From Baseline in Glycoalbumin | At Week 8 | -0.21 Percent | Standard Deviation 2.033 |
Comparison: Change from baseline in glycoalbumin at Week 2 was compared between the treatment groups.95% CI: [-2.184, -1.34]
Comparison: Change from baseline in glycoalbumin at Week 4 was compared between the treatment groups.95% CI: [-3.03, -1.87]
Comparison: Change from baseline in glycoalbumin at Week 8 was compared between the treatment groups.95% CI: [-3.289, -1.679]
Comparison: Change from baseline in glycoalbumin at Week 12 was compared between the treatment groups.95% CI: [-3.608, -1.715]
Comparison: Change from baseline in glycoalbumin at End of Treatment Period I was compared between the treatment groups.95% CI: [-3.608, -1.715]
Secondary
Changes From Baseline in HbA1c
Reported data was the change from baseline in HbA1c at each time point.
Time frame: Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)
Population: Full Analysis Set: All randomized participants who received at least one dose of study drug. The analyzed numbers for each arm were participants who were evaluable for this outcome measure at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 12 | -0.73 Percent HbA1c | Standard Deviation 0.576 |
| Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 4 | -0.46 Percent HbA1c | Standard Deviation 0.37 |
| Trelagliptin 25 mg | Changes From Baseline in HbA1c | At the End of Treatment Period I | -0.70 Percent HbA1c | Standard Deviation 0.555 |
| Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 8 | -0.64 Percent HbA1c | Standard Deviation 0.556 |
| Trelagliptin 25 mg | Changes From Baseline in HbA1c | At the End of Treatment Period II | -0.76 Percent HbA1c | Standard Deviation 0.824 |
| Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 2 | -0.24 Percent HbA1c | Standard Deviation 0.274 |
| Placebo and Trelagliptin 25 mg | Changes From Baseline in HbA1c | At the End of Treatment Period II | -0.74 Percent HbA1c | Standard Deviation 0.843 |
| Placebo and Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 2 | 0.05 Percent HbA1c | Standard Deviation 0.26 |
| Placebo and Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 8 | -0.05 Percent HbA1c | Standard Deviation 0.53 |
| Placebo and Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 12 | 0.03 Percent HbA1c | Standard Deviation 0.74 |
| Placebo and Trelagliptin 25 mg | Changes From Baseline in HbA1c | At the End of Treatment Period I | 0.00 Percent HbA1c | Standard Deviation 0.731 |
| Placebo and Trelagliptin 25 mg | Changes From Baseline in HbA1c | At Week 4 | 0.02 Percent HbA1c | Standard Deviation 0.362 |
Comparison: Change from baseline in HbA1c at Week 2 was compared between the treatment groups.95% CI: [-0.385, -0.18]
Comparison: Change from baseline in HbA1c at Week 4 was compared between the treatment groups.95% CI: [-0.621, -0.338]
Comparison: Change from baseline in HbA1c at Week 8 was compared between the treatment groups.95% CI: [-0.797, -0.367]
Comparison: Change from baseline in HbA1c at Week 12 was compared between the treatment groups.95% CI: [-0.975, -0.441]
Comparison: Change from baseline in HbA1c at End of Treatment Period I was compared between the treatment groups.95% CI: [-0.948, -0.452]
Secondary
Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II
Time frame: At the end of Treatment Period I (Up to Week 12) and Period II (Up to Week 52)
Population: Full Analysis Set: All randomized participants who received at least one dose of study drug. The analyzed numbers for each arm were participants who were evaluable for this outcome measure at the given time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <7.0% at the End of Treatment Period I | 22 Participants |
| Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <8.0% at the End of Treatment Period I | 10 Participants |
| Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <7.0% at the End of Treatment Period II | 22 Participants |
| Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <6.0% at the End of Treatment Period II | 7 Participants |
| Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <8.0% at the End of Treatment Period II | 11 Participants |
| Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <6.0% at the End of Treatment Period I | 3 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <8.0% at the End of Treatment Period II | 8 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <6.0% at the End of Treatment Period I | 2 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <6.0% at the End of Treatment Period II | 8 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <7.0% at the End of Treatment Period I | 7 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <8.0% at the End of Treatment Period I | 5 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II | HbA1c <7.0% at the End of Treatment Period II | 18 Participants |
Comparison: The data of participants achieving \<6.0% at the end of Treatment Period I were compared between the treatment groups.95% CI: [-6.598, 9.919]
Comparison: The data of participants achieving \<7.0% at the end of Treatment Period I were compared between the treatment groups.95% CI: [14.194, 51.66]
Comparison: The data of participants achieving \<8.0% at the end of Treatment Period I were compared between the treatment groups.95% CI: [15.528, 75.7]
Secondary
Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II
Here QTcF is corrected QT interval by Fridericia formula.
Time frame: Up to Week 12
Population: Safety Analysis Set: The safety analysis set was defined as all participants who received at least one dose of the study drug. The analyzed numbers for each arm were participants who were evaluable for this outcome measure at the given time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | QTcF Interval >480 msec | 3 Participants |
| Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | QTcF Interval >450 millisecond (msec) | 13 Participants |
| Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | QTcF Interval >500 msec | 1 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | QTcF Interval >450 millisecond (msec) | 16 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | QTcF Interval >480 msec | 5 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters Before the Start of Study Drug Administration in Treatment Period II | QTcF Interval >500 msec | 1 Participants |
Secondary
Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II
Here U/L is Unit/Litter, and ULN is Upper Limit of Normal.
Time frame: Up to Week 12
Population: Safety Analysis Set: The safety analysis set was defined as all participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II | Amylase (U/L) >2×ULN | 4 Participants |
| Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II | Lipase (U/L) >3×ULN | 1 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II | Amylase (U/L) >2×ULN | 1 Participants |
| Placebo and Trelagliptin 25 mg | Number of Participants With Markedly Abnormal Values of Clinical Laboratory Parameters Before the Start of Study Drug Administration in Treatment Period II | Lipase (U/L) >3×ULN | 3 Participants |
Secondary
Numbers of Participants With TEAE Related to Vital Signs Before the Start of Study Drug Administration in Treatment Period II
Number of participants with a vital sign-related TEAE classified under the System Organ Class of investigations, was reported.
Time frame: Up to Week 12
Population: Safety Analysis Set: The safety analysis set was defined as all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trelagliptin 25 mg | Numbers of Participants With TEAE Related to Vital Signs Before the Start of Study Drug Administration in Treatment Period II | 1 Participants |
| Placebo and Trelagliptin 25 mg | Numbers of Participants With TEAE Related to Vital Signs Before the Start of Study Drug Administration in Treatment Period II | 2 Participants |