Safety and PK of MBX-400 (Cyclopropavir) in Normal Volunteers

NCT ID: NCT02454699

Last Updated: 2017-12-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-10
• Study Completion Date: 2017-12-01

Brief Summary

This is a phase I safety, PK and food effect study of the CMV drug. In part 1 of the study, subjects will receive one of four dosage strengths of MBX-400 (100 mg once daily, 350 mg once daily; 750 mg once daily; and 1000 once daily) for 7 days and safety and PK will be assessed. Subjects must be 18 to 65 years of age, male or female; if female, be surgically-sterilized or post-menopausal; if male, have undergone vasectomy; have a body mass index (BMI) of 18 to 32 kg/m^2; not be a user of nicotine-containing products; be willing to abstain from nicotine-containing products, alcohol and illicit drugs during the study. Subjects will be followed for 28 days post dosing.

Detailed Description

Cytomegalovirus (CMV) is a common cause of viral illness in children and adults. CMV is also an important congenital infection with complications including deafness, developmental delay, and cerebral palsy. The proposed study design is a standard multiple ascending dose escalation study. Four cohorts of 8 subjects each (6 active; 2 placebo) will be enrolled sequentially. MBX-400 will be administered orally once daily for 7 days, in the form of capsules, by study staff while the subject is an inpatient in a research unit. The study doses will be 100, 350, 750, and 1,000 mg daily. Up to 32 healthy male and female (non-pregnant, non-lactating) volunteers ages 18-65 in one site, will be consented and allowed to participate in the study if upon screening they meet the inclusion/exclusion criteria. Subjects will be enrolled into one of four sequential cohorts groups: Cohort 1 will receive 100 mg PO once daily for 7 days, Cohort 2 will receive 350 mg PO once daily for 7 days, Cohort 3 will receive 750 mg PO once daily for 7 days, and Cohort 4 will receive 1000 mg PO once daily for 7 days of MBX-400. Two members of each cohort will receive placebo. The study duration for each subject is expected to be approximately 80 days (screening period, administration of daily dose, and follow-up). Each subject may be admitted to the unit 1 day prior to the first dose, and will remain in the unit until the day after the 7th daily dose. Subjects will return for follow-up visits after the last dose. Safety, tolerability, and pharmacokinetics will be assessed. The overall study duration across all study groups is expected to be approximately 18 months. The primary objective evaluate the safety and tolerability of multiple ascending doses of 100, 350, 750, and 1000 mg PO once daily for 7 days of MBX-400 in healthy subjects. The secondary objective determine the plasma and urine pharmacokinetic profile of multiple doses of 100, 350, 750, and 1000 mg PO once daily for 7 days of MBX-400 in healthy subjects.

Conditions

Cytomegalovirus Infection

Keywords

antiviral; ascending dose; Cytomegalovirus; food effect; Herpesviridae; MBX-400

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1000mg MBX400

6 subjects receive 1000 mg MBX400 orally once per day for 7 days, 2 subjects receive Placebo orally once per day for 7 days

Group Type: EXPERIMENTAL

MBX400

Intervention Type: DRUG

MBX-400, a white to off-white crystalline powder, will be given orally x 7 days to 4 cohorts. Cohort 1 receives 100 mg/day, Cohort 2 receives 350 mg, Cohort 3 receives 750 mg, Cohort 4 receives 1000 mg.

Placebo

Intervention Type: OTHER

Placebo capsules are supplied as white opaque, hard gelatin capsules filled with microcrystalline cellulose. 2 subjects from each cohort receive Placebo orally once per day x 7 days.

100mg MBX400

6 subjects receive 100 mg MBX400 orally once per day for 7 days, 2 subjects receive Placebo orally once per day for 7 days

Group Type: EXPERIMENTAL

MBX400

Intervention Type: DRUG

MBX-400, a white to off-white crystalline powder, will be given orally x 7 days to 4 cohorts. Cohort 1 receives 100 mg/day, Cohort 2 receives 350 mg, Cohort 3 receives 750 mg, Cohort 4 receives 1000 mg.

Placebo

Intervention Type: OTHER

Placebo capsules are supplied as white opaque, hard gelatin capsules filled with microcrystalline cellulose. 2 subjects from each cohort receive Placebo orally once per day x 7 days.

350mg MBX400

6 subjects receive 350 mg MBX400 orally once per day for 7 days, 2 subjects receive Placebo orally once per day for 7 days

Group Type: EXPERIMENTAL

MBX400

Intervention Type: DRUG

MBX-400, a white to off-white crystalline powder, will be given orally x 7 days to 4 cohorts. Cohort 1 receives 100 mg/day, Cohort 2 receives 350 mg, Cohort 3 receives 750 mg, Cohort 4 receives 1000 mg.

Placebo

Intervention Type: OTHER

Placebo capsules are supplied as white opaque, hard gelatin capsules filled with microcrystalline cellulose. 2 subjects from each cohort receive Placebo orally once per day x 7 days.

750mg MBX400

6 subjects receive 750 mg MBX400 orally once per day for 7 days, 2 subjects receive Placebo orally once per day for 7 days

Group Type: EXPERIMENTAL

MBX400

Intervention Type: DRUG

MBX-400, a white to off-white crystalline powder, will be given orally x 7 days to 4 cohorts. Cohort 1 receives 100 mg/day, Cohort 2 receives 350 mg, Cohort 3 receives 750 mg, Cohort 4 receives 1000 mg.

Placebo

Intervention Type: OTHER

Placebo capsules are supplied as white opaque, hard gelatin capsules filled with microcrystalline cellulose. 2 subjects from each cohort receive Placebo orally once per day x 7 days.

Interventions

MBX400

MBX-400, a white to off-white crystalline powder, will be given orally x 7 days to 4 cohorts. Cohort 1 receives 100 mg/day, Cohort 2 receives 350 mg, Cohort 3 receives 750 mg, Cohort 4 receives 1000 mg.

Intervention Type: DRUG

Placebo

Placebo capsules are supplied as white opaque, hard gelatin capsules filled with microcrystalline cellulose. 2 subjects from each cohort receive Placebo orally once per day x 7 days.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Subject is able to provide informed consent; 2. Subject age is between 18 through 65 years of age, inclusive; 3. Good general health as judged by the investigator; 4. Body Mass Index (BMI) between 18 to 32 kg/m^2; 5. Males or females who have either no capability or no sexual behavior that could result in fathering or conceiving a child in the future; Meeting this inclusion criterion would be demonstrated by one of the parameters below: -Surgical sterilization (vasectomy, tubal ligation, or hysterectomy) -Females who are post-menopausal, as defined by the absence of menstrual periods for greater than one year after age 45 without alternate diagnosis (e.g., PCOS) -Absence of any heterosexual activity except with a partner meeting one of the above criteria; 6. Available and willing to participate in the study procedures and requirements; Able and willing to stay in a clinical facility for up to 10 days and return for all visits; swallow the capsules provided; and have blood and urine collections for the duration of the study. 7. Non-smoker, former smoker, or former user of nicotine-containing products Former smoker/user defined as someone who smoked or used nicotine-products one or more times a week for at least one month who has not smoked for at least 3 months and has not used nicotine-containing products for at least 1 month and is willing to abstain from nicotine-containing products during the study; 8. Willing to abstain from alcohol until after Day 10 visit* and should moderate drinking through study end (less than or equal to 2 drinks/day). Illicit drugs should not be used throughout the study; *the completion of PK collections 9. Demonstrates knowledge and comprehension of the study by passing a questionnaire of the study protocol with a score of at least 70%. Anyone not passing the test initially may retake the test once.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, United States

Countries

United States

References

Rouphael NG, Hurwitz SJ, Hart M, Beck A, Anderson EJ, Deye G, Osborn B, Cai SY, Focht C, Amegashie C, Bowlin TL, Brooks J, Mulligan MJ. Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers. Antimicrob Agents Chemother. 2019 Aug 23;63(9):e00717-19. doi: 10.1128/AAC.00717-19. Print 2019 Sep.

Reference Type: DERIVED

PMID: 31285228 (View on PubMed)

Other Identifiers

HHSN272201300018I

Identifier Type: -

Identifier Source: secondary_id

13-0092

Identifier Type: -

Identifier Source: org_study_id