A Phase 1, Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study Investigating the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of CB-0406 Tablets in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- CB-0406 100 mg
- Conditions
- Healthy Volunteers
- Sponsor
- CymaBay Therapeutics, Inc.
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Pharmacokinetic Parameters
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The study is designed as a single center, randomized, double-blind, placebo-controlled study to assess the PK, safety, tolerability and PD of CB-0406 in healthy participants. The study will be conducted as a 2-part study.
Detailed Description
The study is designed as a 2-part study: Part 1 is designed as single ascending dose (SAD) escalation study investigating 5 dose levels. Each cohort will consist of participants (N=8) to be randomly assigned to receive a blinded oral dose of CB-0406 (n=6) or placebo (n=2). Dose levels of CB-0406 in the sequential cohorts will be 100 mg, 200 mg, 400 mg, 800 mg or 1000 mg to be administered once on each cohorts study Day 1. Part 2 is designed as multiple ascending dose (MAD) escalation study investigating up to 5 dose levels as determined by the SAD cohort. Doses will be determined following completion and review of the safety and PK findings for Cohorts 1 to Cohort 5 in Part 1.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for study entry participants must satisfy all of the following criteria:
- •Provide written informed consent before any study specific evaluation is performed;
- •Healthy adult male and female volunteers between the ages of 18 and 65 years, inclusive, at screening;
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- •Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy, tubal ligation or bilateral oophorectomy - verbal confirmation through medical history review acceptable) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient);
- •Of childbearing potential and agrees to use a highly effective method of contraception consistently during the treatment period and for at least 30 days after the dose of study treatment;
- •A male patient with a female partner of childbearing potential is eligible to participate if he and his female partner agrees to use acceptable contraception during the treatment period and for at least 30 days after the last dose of study treatment and refrains from donating sperm during this period.
- •Body mass index of 18.0 to 32.0 kg/m2, inclusive, at screening;
- •Hematology, clinical chemistry, coagulation and urinalysis test results within normal ranges or has no clinically relevant deviations, as determined by the investigator in consultation with sponsor, at screening and Day -
- •Tests with out of range values at screening or Day -1 may be repeated once per assessment point;
Exclusion Criteria
- •Participants will be excluded from the study if one or more of the following criterion are applicable:
- •Has an active or recurring clinically significant disorder of the skin, head, ears, eyes, nose, or throat; an active or recurring clinically significant disorder of the respiratory, cardiovascular, gastrointestinal, endocrine/metabolic, genitourinary, neurologic, hematologic, musculoskeletal, immunologic, or psychological/psychiatric system; or a disease requiring medical treatment;
- •Previous history of any surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of CB-0406, such as stomach or intestinal surgery or resection (e.g., gastrectomy or any type of gastric by-pass surgery or gastric banding procedure);
- •Planning any elective medical treatment or surgery during the trial period or within 30 days of Day -1;
- •Any evidence or treatment of malignancy (other than localized basal cell cancer, squamous cell skin cancer, or cancer in situ that has been resected) within the previous 5 years;
- •Known history of allergic reactions to or have previously received arhalofenate, MBX-102, JNJ39659100, Metaglidasen, and/or K 118;
- •Previous history or evidence at screening of sick sinus syndrome or second- or third-degree atrioventricular block or any cardiac arrhythmia other than a benign sinus arrhythmia. Participant has not had a myocardial infarction within the last 6 months;
- •Clinically significant renal disease, nephrectomy, renal transplant or estimated glomerular filtration rate of \<90 mL/min/1.73 m2 at screening based on Chronic Kidney Disease Epidemiology Collaboration creatinine equation (2009).
- •Blood pressure after resting for at least 5 minutes that is higher than 150 mm Hg systolic or 95 mm Hg diastolic, or lower than 90 mm Hg systolic or 50 mm Hg diastolic at screening or Day -
- •A single repeat measurement at screening or Day -1 is allowed based on the investigator's judgment;
Arms & Interventions
Cohort 1
Cohort 1: 100 mg CB-0406 (n=6)
Intervention: CB-0406 100 mg
Cohort 2
Cohort 2: 200 mg CB-0406 (n=6). Dose initiated following review of all safety data from Cohort 1 by a Safety Review Committee
Intervention: CB-0406 200 mg
Cohort 3
Cohort 3: 400 mg CB-0406 (n=6). Dose initiated following review of all safety data and PK data from Cohort 2 by a Safety Review Committee.
Intervention: CB-0406 400 mg
800 mg
Cohort 4: 800 mg CB-0406 (n=6). Dose initiated following review of all safety data and PK data from Cohort 3 by a Safety Review Committee.
Intervention: CB-0406 800 mg
1000 mg
Cohort 5: 1000 mg CB-0406 (n=6). Dose initiated following review of all safety data and PK data from Cohort 4 by a Safety Review Committee
Intervention: CB-0406 1,000 mg
Matched placebo
Two subjects in each Cohort (1, 2, 3, 4, 5) are randomized to matched placebo
Intervention: Matched placebo
Outcomes
Primary Outcomes
Pharmacokinetic Parameters
Time Frame: Part 1: Day 1 to Day 15; Part 2: Day 14 to Day 28
Concentration of CB-0406 in plasma.
Secondary Outcomes
- Incidence of Treatment-Emergent Adverse Events(Part 1: Day 1 to Day 22; Part 2: Day 1 to Day 35)
- Incidence of Abnormal Vital Signs(Part 1: Every visit; Part 2 Every visit)
- Incidence of Abnormal ECGs(Part 1: Screening, Day 1, Day 2, Day 3, Day 4, Day 9, Day 15, EOS/ET; Part 2 Screening, Day 1, Day 2 to 13, Day 14, Day 16, Day 20, Day 28, Day 35)
- Pharmacodynamic Activity(Part 1: Day 1 to Day 15; Part 2: Day 14 to Day 28)
- Incidence of abnormal laboratory tests results(Part 1: Screening, Day -1, Day 2, Day 4, Day 9, Day 15, EOS/ET Part 2: Screening, Day -1, Day 2 to 13, Day 14, Day 16, Day 20, Day 28, EOS/ET)
- Incidence of Abnormal Physical Exams(Part 1: Day -1 and at the EOS/ET visit; Part 2 Screening, Day 1, Day 2 to 13, Day 4, Day 16, Day 20, Day 28, EOS/ET)