Dyslipidemia
Conditions
Brief summary
A study to evaluate the efficacy of K-877 extended release (ER) once daily (QD) compared to K-877 immediate release (IR) twice daily (BID).
Interventions
DRUGK-877-ER (Dose A)
Dose A Oral Administration
DRUGK-877-ER (Dose B)
Dose B Oral Administration
DRUGK-877-IR
K-877-IR Oral Administration
Sponsors
Kowa Research Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to provide written informed consent before any study-specific evaluation is performed * At screening, have a mean fasting TG level of ≥180 mg/dL and \<550 mg/dL; at subsequent Qualification Period visits confirm fasting TG level of ≥200 mg/dL and \<500 mg/dL * Able to meet all inclusion criteria outlined in clinical study protocol
Exclusion criteria
* Require lipid-altering treatments other than study drugs, statins, ezetimibe, or PCSK9 inhibitors during the study * Known hypersensitivity or intolerance to fibrates or peroxisome proliferator-activated receptor alpha agonists * Meet any other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Estimated Percentage Change in Fasting Triglyceride(s) (TG) | Baseline to Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline to Day 28 in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline to Day 28 | — |
| Percentage Change From Baseline to Day 28 in High-density Lipoprotein Cholesterol (HDL-C) | Baseline to Day 28 | — |
| Percentage Change From Baseline to Day 28 in Remnant Cholesterol | Baseline to Day 28 | — |
| Percentage Change From Baseline to Day 28 in Total Cholesterol (TC) | Baseline to Day 28 | — |
| Percentage Change From Baseline to Day 28 in Free Fatty Acid (FFAs) | Baseline to Day 28 | — |
| K-877 PK Parameters Cmax | Day 28 | Observed maximum measured plasma concentration (Cmax) |
| K-877 PK Parameters AUC (Tau) | Day 28 | — |
| Percentage Change From Baseline to Day 28 in Non-HDL-C | Baseline to Day 28 | — |
Countries
United States
Participant flow
Pre-assignment details
The Screening Period occurred no more than 70 days and no less than 7 days prior to the first dose of study drug. The up to 10-week Screening Period allowed for a 6-week washout period, if needed, followed by an up to 4-week Qualification Period that was used to assess patient eligibility. Prior to treatment on Day 1, eligible patients were randomized in a 1:1:1 ratio to 1 of 3 treatment groups. Randomization was stratified by sex, statin use, and PK assessment.
Participants by arm
| Arm | Count |
|---|---|
| K-877-IR K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28. | 32 |
| K-877-ER Dose A K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28. | 32 |
| K-877-ER Dose B K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28. | 32 |
| Total | 96 |
Baseline characteristics
| Characteristic | Total | K-877-IR | K-877-ER Dose A | K-877-ER Dose B |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 8 Participants | 6 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 72 Participants | 24 Participants | 26 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 7 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 24 Participants | 23 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 93 Participants | 31 Participants | 31 Participants | 31 Participants |
| Sex: Female, Male Female | 44 Participants | 15 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Male | 52 Participants | 17 Participants | 17 Participants | 18 Participants |
| Statin Use No | 51 Participants | 17 Participants | 17 Participants | 17 Participants |
| Statin Use Yes | 45 Participants | 15 Participants | 15 Participants | 15 Participants |
| TG at Baseline | 293.65 mg/dL STANDARD_DEVIATION 63.915 | 278.72 mg/dL STANDARD_DEVIATION 53.316 | 294.88 mg/dL STANDARD_DEVIATION 61.949 | 307.35 mg/dL STANDARD_DEVIATION 73.575 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 1 / 32 | 5 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Estimated Percentage Change in Fasting Triglyceride(s) (TG)
Time frame: Baseline to Day 28
Population: The Per-Protocol Set (PPS) was defined as all patients in the Full Analysis Set without any major protocol deviations and who had baseline and Day 28 fasting serum TG measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Estimated Percentage Change in Fasting Triglyceride(s) (TG) | -41.57 Percent Change | Standard Deviation 3.295 |
| K-877-ER Dose A | Estimated Percentage Change in Fasting Triglyceride(s) (TG) | -36.79 Percent Change | Standard Deviation 3.319 |
| K-877-ER Dose B | Estimated Percentage Change in Fasting Triglyceride(s) (TG) | -38.94 Percent Change | Standard Deviation 3.553 |
p-value: 0.3084Mixed Model for repeated measures (MMRM)
p-value: 0.593Mixed Model for repeated measures (MMRM)
Secondary
K-877 PK Parameters AUC (Tau)
Time frame: Day 28
Population: The PK Analysis Set included all patients from the Safety Analysis Set who had at least 1 PK sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | K-877 PK Parameters AUC (Tau) | 10.239 h-ng/mL | Geometric Coefficient of Variation 43.1 |
| K-877-ER Dose A | K-877 PK Parameters AUC (Tau) | 22.566 h-ng/mL | Geometric Coefficient of Variation 71.3 |
| K-877-ER Dose B | K-877 PK Parameters AUC (Tau) | 41.611 h-ng/mL | Geometric Coefficient of Variation 44.1 |
Secondary
K-877 PK Parameters Cmax
Observed maximum measured plasma concentration (Cmax)
Time frame: Day 28
Population: The PK Analysis Set included all patients from the Safety Analysis Set who had at least 1 PK sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | K-877 PK Parameters Cmax | 2.061 ng/mL | Geometric Coefficient of Variation 63.9 |
| K-877-ER Dose A | K-877 PK Parameters Cmax | 2.746 ng/mL | Geometric Coefficient of Variation 85.2 |
| K-877-ER Dose B | K-877 PK Parameters Cmax | 5.433 ng/mL | Geometric Coefficient of Variation 61.2 |
Secondary
Percentage Change From Baseline to Day 28 in Free Fatty Acid (FFAs)
Time frame: Baseline to Day 28
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Percentage Change From Baseline to Day 28 in Free Fatty Acid (FFAs) | -7.35 Percent Change | Standard Deviation 45.11 |
| K-877-ER Dose A | Percentage Change From Baseline to Day 28 in Free Fatty Acid (FFAs) | -17.17 Percent Change | Standard Deviation 25.43 |
| K-877-ER Dose B | Percentage Change From Baseline to Day 28 in Free Fatty Acid (FFAs) | -10.22 Percent Change | Standard Deviation 40.436 |
p-value: 0.2562MMRM
p-value: 0.4268MMRM
Secondary
Percentage Change From Baseline to Day 28 in High-density Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline to Day 28
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Percentage Change From Baseline to Day 28 in High-density Lipoprotein Cholesterol (HDL-C) | 12.22 Percent Change | Standard Deviation 27.335 |
| K-877-ER Dose A | Percentage Change From Baseline to Day 28 in High-density Lipoprotein Cholesterol (HDL-C) | 15.39 Percent Change | Standard Deviation 18.19 |
| K-877-ER Dose B | Percentage Change From Baseline to Day 28 in High-density Lipoprotein Cholesterol (HDL-C) | 20.04 Percent Change | Standard Deviation 24.37 |
p-value: 0.9353MMRM
p-value: 0.3099MMRM
Secondary
Percentage Change From Baseline to Day 28 in Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline to Day 28
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Percentage Change From Baseline to Day 28 in Low-density Lipoprotein Cholesterol (LDL-C) | 3.56 Percent Change | Standard Deviation 28.586 |
| K-877-ER Dose A | Percentage Change From Baseline to Day 28 in Low-density Lipoprotein Cholesterol (LDL-C) | -2.16 Percent Change | Standard Deviation 21.394 |
| K-877-ER Dose B | Percentage Change From Baseline to Day 28 in Low-density Lipoprotein Cholesterol (LDL-C) | 22.71 Percent Change | Standard Deviation 64.42 |
p-value: 0.884MMRM analysis
p-value: 0.1202MMRM analysis
Secondary
Percentage Change From Baseline to Day 28 in Non-HDL-C
Time frame: Baseline to Day 28
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Percentage Change From Baseline to Day 28 in Non-HDL-C | -10.04 Percent Change | Standard Deviation 21.704 |
| K-877-ER Dose A | Percentage Change From Baseline to Day 28 in Non-HDL-C | -11.12 Percent Change | Standard Deviation 18.847 |
| K-877-ER Dose B | Percentage Change From Baseline to Day 28 in Non-HDL-C | -3.74 Percent Change | Standard Deviation 21.394 |
p-value: 0.5647MMRM
p-value: 0.217MMRM
Secondary
Percentage Change From Baseline to Day 28 in Remnant Cholesterol
Time frame: Baseline to Day 28
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Percentage Change From Baseline to Day 28 in Remnant Cholesterol | -33.85 Percentage Change | Standard Deviation 32.467 |
| K-877-ER Dose A | Percentage Change From Baseline to Day 28 in Remnant Cholesterol | -30.08 Percentage Change | Standard Deviation 25.394 |
| K-877-ER Dose B | Percentage Change From Baseline to Day 28 in Remnant Cholesterol | -32.34 Percentage Change | Standard Deviation 24.761 |
p-value: 0.2098MMRM
p-value: 0.3688MMRM
Secondary
Percentage Change From Baseline to Day 28 in Total Cholesterol (TC)
Time frame: Baseline to Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K-877-IR | Percentage Change From Baseline to Day 28 in Total Cholesterol (TC) | -6.07 Percent Change | Standard Deviation 15.417 |
| K-877-ER Dose A | Percentage Change From Baseline to Day 28 in Total Cholesterol (TC) | -8.68 Percent Change | Standard Deviation 13.266 |
| K-877-ER Dose B | Percentage Change From Baseline to Day 28 in Total Cholesterol (TC) | 0.28 Percent Change | Standard Deviation 18.1 |
p-value: 0.9788MMRM
p-value: 0.1314MMRM