A Phase 1, Single-Center, Double-Blind, Randomized, Placebo- and Positive Controlled, Double-Dummy, Parallel-Group, Repeated Dose Study With a Nested Cross-Over Comparison Between Moxifloxacin and Placebo to Evaluate the Effect of MD1003 on Cardiac Repolarization in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- MD1003
- Conditions
- Healthy Volunteers
- Sponsor
- MedDay Pharmaceuticals SA
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Change from baseline QTcF (ΔQTcF) on Day 8 (after 8 days of 1200 mg MD1003)
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a Phase 1, single-center, double-blind, randomized, placebo- and positive controlled, double-dummy, parallel-group, repeated-dose study with a nested cross-over comparison between moxifloxacin and placebo to evaluate the effect of MD1003 on cardiac repolarization in healthy adult subjects.
The planned enrollment is approximately 64 subjects randomized in a ratio of 1:1 to 2main groups. Subjects in Group B will be further randomized to Subgroups B1 and B2 in a ratio of 1:1.
Detailed Description
This study is designed as a definitive evaluation of the potential of MD1003 and its major metabolites to have a threshold effect on cardiac repolarization, as detected by QT/QTc prolongation. The design is aligned with the recommendations for evaluation of QT/QTc interval prolongation outlined in the International Council for Harmonization (ICH) E14 guidance. This is a Phase 1, single-center, double-blind, randomized, placebo- and positive controlled, double-dummy, parallel-group, repeated-dose study with a nested cross-over comparison between moxifloxacin and placebo to evaluate the effect of MD1003 on cardiac repolarization in healthy adult subjects. A total of 64 subjects will be enrolled in the clinical study according to the inclusion/exclusion criteria. The study consists of two main groups with 32 subjects per dose group. All subjects will receive placebo for MD1003 on Day -1. Subjects in Group A will receive MD1003 (biotin) 1200 mg and placebo for moxifloxacin on Day 1, MD1003 (biotin) 1200 mg from Day 2 through Day 8 and placebo for moxifloxacin on Day 9. Subjects in Group B will be further randomized to Subgroup B1 (16 subjects) receiving moxifloxacin 400 mg and placebo for MD1003 on Day 1, placebo for MD1003 from Day 2 through Day 8 and placebo for moxifloxacin on Day 9. Subgroup B2 (16 subjects) will receive placebo for moxifloxacin and placebo for MD1003 on Day 1, placebo for MD1003 from Day 2 through Day 8 and moxifloxacin 400 mg on Day 9.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form prior to performing any of the Screening Visit procedures.
- •Males and females between 18 to 55 years of age, inclusive, at the Screening Visit.
- •Female subjects of childbearing potential must not be planning to become pregnant, must not be breastfeeding, and must have a negative serum pregnancy test at Screening and negative urine pregnancy test on Day-
- •Sexually active female subjects of childbearing potential (i.e. women who are not post-menopausal \[12 months of spontaneous amenorrhea without an alternative medical cause and follicle stimulating hormone (FSH) levels in the post-menopausal range for the laboratory involved\] or who have not had a documented hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) and all male subjects (who have not been surgically sterilized by documented vasectomy) must agree to use highly effective methods of contraception during the study and for 8 weeks after the last dose of study drug. Please refer to Section 5.4.4 for acceptable methods of contraception.
- •Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the screening.
- •Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at the Screening Visit.
- •Healthy adult subjects with suitable veins for cannulation.
- •Healthy, determined by pre-study medical evaluation (medical history, renal function, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations).
- •Supine vital signs should be within the normal range at Screening and Day -2:
- •oral body temperature between 35.0°C - 37.5°C;
Exclusion Criteria
- Not provided
Arms & Interventions
Group A-MD1003
Group A=32 subjects Placebo for MD1003 on Day -1. Daily dose of 1200 mg of MD1003 from Day 1 to Day 8 Placebo for moxifloxacin on Day 1 and Day 9
Intervention: MD1003
Group A-MD1003
Group A=32 subjects Placebo for MD1003 on Day -1. Daily dose of 1200 mg of MD1003 from Day 1 to Day 8 Placebo for moxifloxacin on Day 1 and Day 9
Intervention: Placebo for MD1003
Group A-MD1003
Group A=32 subjects Placebo for MD1003 on Day -1. Daily dose of 1200 mg of MD1003 from Day 1 to Day 8 Placebo for moxifloxacin on Day 1 and Day 9
Intervention: Placebo for moxifloxacin
Group B-Moxifloxacin
Subjects in Group B will be further randomized to Subgroups B1 and B2 in a ratio of 1:1. Subgroup B1: 16 subjects Placebo for MD1003 on Day -1 Placebo for MD1003 from Day 1 to Day 8 Moxifloxacin 400 mg on Day 1 and Placebo for moxifloxacin on Day 9 Subgroup B2: 16 subjects Placebo for MD1003 on Day -1 Placebo for MD1003 from Day 1 to Day 8 Placebo for moxifloxacin on Day 1 and Moxifloxacin 400 mg on Day 9
Intervention: Moxifloxacin 400mg
Group B-Moxifloxacin
Subjects in Group B will be further randomized to Subgroups B1 and B2 in a ratio of 1:1. Subgroup B1: 16 subjects Placebo for MD1003 on Day -1 Placebo for MD1003 from Day 1 to Day 8 Moxifloxacin 400 mg on Day 1 and Placebo for moxifloxacin on Day 9 Subgroup B2: 16 subjects Placebo for MD1003 on Day -1 Placebo for MD1003 from Day 1 to Day 8 Placebo for moxifloxacin on Day 1 and Moxifloxacin 400 mg on Day 9
Intervention: Placebo for MD1003
Group B-Moxifloxacin
Subjects in Group B will be further randomized to Subgroups B1 and B2 in a ratio of 1:1. Subgroup B1: 16 subjects Placebo for MD1003 on Day -1 Placebo for MD1003 from Day 1 to Day 8 Moxifloxacin 400 mg on Day 1 and Placebo for moxifloxacin on Day 9 Subgroup B2: 16 subjects Placebo for MD1003 on Day -1 Placebo for MD1003 from Day 1 to Day 8 Placebo for moxifloxacin on Day 1 and Moxifloxacin 400 mg on Day 9
Intervention: Placebo for moxifloxacin
Outcomes
Primary Outcomes
Change from baseline QTcF (ΔQTcF) on Day 8 (after 8 days of 1200 mg MD1003)
Time Frame: 9 days
Replicate electrocardiograms (ECGs) (10 ECG replicates) for the determination of ΔQTc interval will be extracted from the continuous digital 12-lead ECG recording in the 5 minutes prior to dosing and then at 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose on D-1 and D8
Secondary Outcomes
- U-waves presence(8 days)
- Placebo-corrected, change from baseline of Pulse Rate (ΔΔPR) on Day 8 (after 8 days of 1200 mg MD1003)(8 days)
- Placebo-corrected, change from baseline of QRS interval (ΔΔQRS) on Day 8 (after 8 days of 1200 mg MD1003)(8 days)
- Maximum plasma concentrations (Cmax) of MD1003 will be measured at D1 and D8 post-dose (after 8 days of dosing of 1200mg of MD1003)(8 days)
- Placebo-corrected change from baseline QTcF (ΔΔQTcF) on Day 8 (after 8 days of 1200 mg MD1003)(9 days)
- Change from baseline of Heart Rate (ΔHR) on Day 8 (after 8 days of 1200 mg MD1003)(9 days)
- Area under the curve (AUC max) of MD1003 will be measured at D1 and D8 post-dose (after 8 days of dosing of 1200mg of MD1003)(8 days)
- Placebo-corrected, change from baseline of Heart Rate (ΔΔHR) on Day 8 (after 8 days of 1200 mg MD1003)(9 days)
- T-wave morphology(8 days)
- Change from baseline of Pulse Rate (ΔPR) on Day 8 (after 8 days of 1200 mg MD1003)(8 days)
- Change from baseline of QRS interval (ΔQRS) on Day 8 (after 8 days of 1200 mg MD1003)(8 days)
- Time for maximum plasma concentration (tmax) of MD1003 will be determined directly from the concentration-time profile(8 days)