TQT2 Study to Evaluate the Effect of MD1003 on Cardiac Repolarization in Healthy Adult Subjects

NCT04168723 | Unknown Phase 1

• 1 other identifier: MD1003CT2019-04TQT2
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Change from baseline QTcF (ΔQTcF) on Day 8 (after 8 days of 1200 mg MD1003)

  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

  9 days

Secondary Outcomes (12)

• 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

• Placebo-corrected, change from baseline of Heart Rate (ΔΔHR) on Day 8 (after 8 days of 1200 mg MD1003)

  9 days

• Change from baseline of Pulse Rate (ΔPR) on Day 8 (after 8 days of 1200 mg MD1003)

  8 days

• Placebo-corrected, change from baseline of Pulse Rate (ΔΔPR) on Day 8 (after 8 days of 1200 mg MD1003)

  8 days

Study Arms (2)

Group A-MD1003

EXPERIMENTAL

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

Drug: MD1003; Drug: Placebo for MD1003; Drug: Placebo for moxifloxacin

Group B-Moxifloxacin

ACTIVE COMPARATOR

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

Drug: Moxifloxacin 400mg; Drug: Placebo for MD1003; Drug: Placebo for moxifloxacin

Interventions

MD1003 DRUG

Group A: Daily dose of 1200 mg of MD1003 from Day 1 to Day 8

Also known as: Biotin

Group A-MD1003

Moxifloxacin 400mg DRUG

Group B1: Moxifloxacin 400 mg on Day 1 Group B2: Moxifloxacin 400 mg on Day 9

Also known as: Moxifloxacin

Group B-Moxifloxacin

Placebo for MD1003 DRUG

Group A: Placebo for MD1003 on Day -1 Group B1: Placebo for MD1003 on Day -1 Group B2: Placebo for MD1003 on Day -1

Group A-MD1003; Group B-Moxifloxacin

Placebo for moxifloxacin DRUG

Group A: Placebo for moxifloxacin on Day 1 and Day 9 Group B1: Placebo for moxifloxacin on Day 9 Group B2: Placebo for moxifloxacin on Day 1

Group A-MD1003; Group B-Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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-2.
• 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;
• systolic BP, 90 - 140 mm Hg;
• diastolic BP, 40 - 90 mm Hg;
• pulse rate, 40 - 100 bpm.
• Subjects should have serum potassium, calcium, and magnesium levels within the normal range at Screening and at admission on Day -2 (morning in fasted condition).
• Subjects should fulfil the following ECG parameters criteria at Screening and Day -2:

You may not qualify if:

• Subject has clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological or psychiatric disorder(s) as determined by the Principal Investigator or designee.
• Subject has any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs.
• Subject has any concurrent disease or condition that, in the opinion of the Principal Investigator, would make the subject unsuitable for participation in the clinical study.
• History or presence of:
• risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome);
• sick sinus syndrome, Mobitz 2second, or third-degree atrioventricular block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval QTc\>450 male/470 female), or conduction abnormalities;
• repeated or frequent syncope or vasovagal episodes;
• hypertension, angina, bradycardia, or severe peripheral arterial circulatory disorders.
• Subjects with serum creatinine clearance below 90 mL/min.
• Subject has history of alcohol and/or illicit drug abuse within 2 years prior to the first dose of study drug.
• Subject has positive test for Hepatitis B surface antigen, Hepatitis C antibody or human immunodeficiency virus antibody at the screening visit.
• Subject has positive urine drug (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids), alcohol or cotinine test at the Screening Visit or Day -2. Consumption of alcohol and alcohol-containing foods, medications or beverages 48 hours prior to the screening visit.
• Female subjects are breastfeeding or female subjects with a positive serum pregnancy test at the Screening Visit or positive urine pregnancy test on Day -2.
• Has had surgery or any medical condition which may affect the absorption, distribution, metabolism, or elimination of the study drugs within 6 months prior to the first dose, in the opinion of the Principal Investigator.
• Plasma donation within 7 days prior to the first dose of study drug.

Sponsors & Collaborators

• MedDay Pharmaceuticals SA: lead
• Parexel: collaborator
• ERT: Clinical Trial Technology Solutions: collaborator

Study Sites (1)

Parexel Early Phase Clinical Unit London

London, Middlesex, HA13UJ, United Kingdom

RECRUITING

MeSH Terms

Interventions

Biotin; Moxifloxacin

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Muna Albayaty, MD

  Parexel Early Phase Clinical Unit London,Northwick Park Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abdelkarim Bendarraz

CONTACT

+33 1 80 40 14 39; Abdabdelkarim.bendarraz@medday-pharma.com

Delphine Bernard

CONTACT

+33 1 80 40 14 47; delphine.bernard@medday-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-Blind, Randomized, Placebo- and Positive Controlled, Double-Dummy, Parallel-Group, Repeated-Dose Study with a Nested Cross-Over Comparison Between Moxifloxacin and Placebo

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 19, 2019
• Study Start: November 11, 2019
• Primary Completion: March 5, 2020
• Study Completion: March 5, 2020
• Last Updated: February 20, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)