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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04467684




Registration number
NCT04467684
Ethics application status
Date submitted
29/06/2020
Date registered
13/07/2020
Date last updated
11/06/2021

Titles & IDs
Public title
Study Investigating the Safety, Tolerability, and PK, PD, of CB-0406
Scientific title
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
Secondary ID [1] 0 0
CB0406-12047
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CB-0406 100 mg
Treatment: Drugs - CB-0406 200 mg
Treatment: Drugs - CB-0406 400 mg
Treatment: Drugs - CB-0406 800 mg
Treatment: Drugs - CB-0406 1,000 mg
Treatment: Drugs - Matched placebo

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

Experimental: 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

Experimental: 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.

Experimental: 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.

Experimental: 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

Placebo comparator: Matched placebo - Two subjects in each Cohort (1, 2, 3, 4, 5) are randomized to matched placebo


Treatment: Drugs: CB-0406 100 mg
Single oral dose

Treatment: Drugs: CB-0406 200 mg
Single oral dose

Treatment: Drugs: CB-0406 400 mg
Single oral dose

Treatment: Drugs: CB-0406 800 mg
Single oral dose

Treatment: Drugs: CB-0406 1,000 mg
Single oral dose

Treatment: Drugs: Matched placebo
Color and size matched placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetic Parameters
Timepoint [1] 0 0
Part 1: Day 1 to Day 15; Part 2: Day 14 to Day 28
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events
Timepoint [1] 0 0
Part 1: Day 1 to Day 22; Part 2: Day 1 to Day 35
Secondary outcome [2] 0 0
Pharmacodynamic Activity
Timepoint [2] 0 0
Part 1: Day 1 to Day 15; Part 2: Day 14 to Day 28
Secondary outcome [3] 0 0
Incidence of abnormal laboratory tests results
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Incidence of Abnormal Vital Signs
Timepoint [4] 0 0
Part 1: Every visit; Part 2 Every visit
Secondary outcome [5] 0 0
Incidence of Abnormal ECGs
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Incidence of Abnormal Physical Exams
Timepoint [6] 0 0
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

Eligibility
Key inclusion criteria
To be eligible for study entry participants must satisfy all of the following criteria:

1. Provide written informed consent before any study specific evaluation is performed;
2. Healthy adult male and female volunteers between the ages of 18 and 65 years, inclusive, at screening;
3. 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;
4. 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.
5. Body mass index of 18.0 to 32.0 kg/m2, inclusive, at screening;
6. 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;
7. 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;
8. 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.
9. Agree to not engage in heavy exercise (e.g., marathon runners, weight-lifting) within 1 week prior to dosing until the final study visit.
10. Able and willing to comply with the protocol and study procedures;
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded from the study if one or more of the following criterion are applicable:

1. 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;
2. 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);
3. Planning any elective medical treatment or surgery during the trial period or within 30 days of Day -1;
4. 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;
5. Known history of allergic reactions to or have previously received arhalofenate, MBX-102, JNJ39659100, Metaglidasen, and/or K 118;
6. 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;
7. 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).
8. 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;
9. 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;
10. History of drug or alcohol abuse within the last 2 years;
11. 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;
12. 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.
13. 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.
14. Received an investigational drug within 30 days or 5 half -lives (whichever is longer) prior to Day 1.
15. Donated more than 450 mL of blood within 30 days prior to Day 1;
16. Evidence of clinically significant hepatic impairment including alanine aminotransferase or aspartate aminotransferase >1.5 times the upper limit of normal, with the exception of elevated bilirubin due to Gilbert's syndrome based on bilirubin fractionation at screening;
17. Positive test result at screening for human immunodeficiency virus (Types 1 or 2) antibody, hepatitis B surface antigen, or hepatitis C virus antibody;
18. Clinically significant acute illness within 4 weeks or other illness deemed to be significant by investigator with agreement of sponsor within 5 days before Day 1;
19. Participant or a family member of the participant is a member of the professional or ancillary personnel working at the investigative site involved in the study;
20. Participant, in the opinion of the investigator, should not participate in the study;
21. Participant has received blood products within 2 months prior to Day -1.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/06/2021
Sample size
Target
Accrual to date
Final
90
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3181 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04467684
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Elaine Watkins, DO, MSPH
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04467684