Study Investigating the Safety, Tolerability, and PK, PD, of CB-0406

NCT04467684 | Completed Phase 1

• 1 other identifier: CB0406-12047
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

single ascending dose (SAD); multiple ascending dose (MAD); CymaBay; CB-0406; arhalofenate; peroxisome proliferator-activated receptor gamma

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic Parameters

  Concentration of CB-0406 in plasma.

  Part 1: Day 1 to Day 15; Part 2: Day 14 to Day 28

Secondary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events

  Part 1: Day 1 to Day 22; Part 2: Day 1 to 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 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

Study Arms (6)

Cohort 1

EXPERIMENTAL

Cohort 1: 100 mg CB-0406 (n=6)

Drug: CB-0406 100 mg

Cohort 2

EXPERIMENTAL

Cohort 2: 200 mg CB-0406 (n=6). Dose initiated following review of all safety data from Cohort 1 by a Safety Review Committee

Drug: CB-0406 200 mg

Cohort 3

EXPERIMENTAL

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.

Drug: CB-0406 400 mg

800 mg

EXPERIMENTAL

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.

Drug: CB-0406 800 mg

1000 mg

EXPERIMENTAL

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

Drug: CB-0406 1,000 mg

Matched placebo

PLACEBO COMPARATOR

Two subjects in each Cohort (1, 2, 3, 4, 5) are randomized to matched placebo

Drug: Matched placebo

Interventions

CB-0406 100 mg DRUG

Single oral dose

Cohort 1

CB-0406 200 mg DRUG

Single oral dose

Cohort 2

CB-0406 400 mg DRUG

Single oral dose

Cohort 3

CB-0406 800 mg DRUG

Single oral dose

800 mg

CB-0406 1,000 mg DRUG

Single oral dose

1000 mg

Matched placebo DRUG

Color and size matched placebo

Matched placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 -1. Tests with out of range values at screening or Day -1 may be repeated once per assessment point;
• No clinically significant abnormalities noted in medical history; or discovered by physical examination, ECG assessment, or measurement of vital signs at screening and Day -1;
• Able and willing to abstain from alcohol, caffeine or caffeine-containing products, grapefruit or grapefruit juice, St John's wort, and herbal supplements for from 24 hours before Day -1 until the end of the confinement period and for 24 hours prior to additional visits to the study site.
• Agree to not engage in heavy exercise (e.g., marathon runners, weight-lifting) within 1 week prior to dosing until the final study visit.
• Able and willing to comply with the protocol and study procedures;

You may not qualify if:

• 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 -1. A single repeat measurement at screening or Day -1 is allowed based on the investigator's judgment;
• Pulse rate obtained from vital signs after resting for 5 minutes that is outside the range of 45 to 90 beats per minute at screening or Day -1. A single repeat measurement is allowed at screening and Day -1 for eligibility based on the investigator's judgment;
• History of drug or alcohol abuse within the last 2 years;
• Positive screen for drugs of abuse (amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinol), tricyclic antidepressants, cotinine or alcohol at screening or Day -1;
• Smoke more than 2 cigarettes per week and have a positive cotinine test at screening or Day -1. Participants must agree to refrain from smoking from 24 hours prior to Day -1 until completion of the end of study (EOS) visit.
• Used or are using prescription or over-the-counter medications, dietary/nutritional supplements (except for multivitamins at the recommended dose and paracetamol, up to 2g in any one day) within 14 days prior to Day 1 and for the duration of the trial.
• Received an investigational drug within 30 days or 5 half -lives (whichever is longer) prior to Day 1.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3181, Australia

Location

Related Publications (2)

• Aronow WS, Harding PR, Khursheed M, Vangrow JS, Papageorge's NP, Mays J. Effect of halofenate on serum lipids. Clin Pharmacol Ther. 1973 May-Jun;14(3):358-65. doi: 10.1002/cpt1973143358. No abstract available.

  PMID: 4572798 BACKGROUND

• Dujovne CA, Azarnoff DL, Pentikainen P, Manion C, Hurwitz A, Hassanein K. A two-year crossover therapeutic trial with halofenate and clofibrate. Am J Med Sci. 1976 Nov-Dec;272(3):277-84. doi: 10.1097/00000441-197611000-00005.

  PMID: 797258 BACKGROUND

Related Links

• CymaBay Therapeutics

Study Officials

• Elaine Watkins, DO, MSPH

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The assignment to either CB-0406 or placebo will be blinded to the participants, investigators and staff at the study site. The pharmacy team will be unblinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: July 13, 2020
• Study Start: July 7, 2020
• Primary Completion: May 30, 2021
• Study Completion: June 6, 2021
• Last Updated: June 11, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)