Phase 1, QT/QTC Interval Study in Healthy Subjects

A Phase 1, Randomized, Placebo and Active Controlled, Double-Blind, Parallel, Electrocardiogram Study to Evaluate the Effect of Lumacaftor in Combination With Ivacaftor on the QT/QTc Interval in Healthy Subjects

This study is designed to evaluate the effect of multiple doses of lumacaftor in combination with ivacaftor on cardiac repolarization, as detected by QT/QTc interval corrected for heart rate in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ivacaftor; Drug: Lumacaftor; Drug: Lumacaftor Placebo; Drug: Ivacaftor Placebo; Drug: moxifloxacin hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must be willing and able to comply with scheduled visits, treatment plan, lifestyle guidelines, laboratory tests, contraceptive guidelines, and other study procedures.
• Subjects must be healthy, as defined by no clinically relevant abnormalities identified by a detailed medical history, physical examination, including blood pressure and pulse rate measurement, and 12 lead ECG.
• Subjects must weigh >50kg

Exclusion Criteria:

• Abnormal renal function at Screening
• Plasma donation within 7 days before first study drug dose or blood donation of 1 pint (500mL) within 56 days before first study drug dose
• Positively screen for Hepatitis B, Hepatitis C, HIV
• Known hypersensitivity or prior adverse reaction to moxifloxacin or other quinolones
• Any condition possibly affecting drug absorption (e.g., gastrectomy, or other gastrointestinal tract surgery, except appendectomy or cholecystectomy or polypectomy) or regular use of acid-lowering therapies (H2 blockers, proton pump inhibitors, and antacids).
• Female subjects who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last study drug dose and female subjects of childbearing potential who are unwilling or unable to follow the contraceptive guidelines from at least 14 days before the first study drug dose.
• Male subject who has a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last study drug dose; male subjects who are unwilling or unable to follow the contraceptive guidelines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A; Will consist of up to 4 cohorts with subjects receiving lumacaftor or placebo for 7 days. Cohort 1: 600 mg lumacaftor once a day Cohort 2: 1000 mg lumacaftor once a day Cohort 3: 1200 mg lumacaftor once a day	Drug: Lumacaftor; Other Names: VX-809; Drug: Lumacaftor Placebo
EXPERIMENTAL: Part B; Will consist of 3 cohorts. All cohorts will be dosed in parallel. Cohort A will receive 600 mg Lumacaftor once a day plus 250 mg Ivacaftor twice a day for 7 days. From day 8-14 subjects will receive a supratherapeutic dose of Lumacaftor (TBD) plus 450 mg Ivacaftor twice a day. Cohort B will receive lumacaftor and ivacaftor matching placebo for 14 days Cohort C will receive a single dose of 400 mg moxifloxacin on day 14	Drug: Ivacaftor; Other Names: VX-770; Drug: Lumacaftor; Other Names: VX-809; Drug: Lumacaftor Placebo; Drug: Ivacaftor Placebo; Drug: moxifloxacin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
(Part A) Safety and tolerability of lumacaftor as measured by standard 12-lead ECGs, adverse events (AEs), vital signs, spirometry, and clinically significant laboratory assessments	7 days
(Part B) Time matched, baseline-adjusted change in QTcF intervals obtained from a continuous ECG recording over a 24 hour interval after administration of a therapeutic and supratherapeutic dose of lumacaftor in combination with ivacaftor	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
(Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC	up to 11 days
(Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin	up to 14 days
(Part B) Time-matched, baseline-adjusted non-QT interval parameters obtained from a continuous ECG recording over a 24-hour interval	up to 14 days
(Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC	up to 15 days
(Part B) PK/PD relationship between plasma concentration and QT/QTc interval	up to 14 days
(Part B) Safety and tolerability of lumacaftor in combination with ivacaftor as measured by standard 12-lead ECGs, AEs, vital signs, and clinical significant laboratory results	up to 24 days

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: July 19, 2013
• First Submitted That Met QC Criteria: July 24, 2013
• First Posted (ESTIMATE): July 29, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 11, 2014
• Last Update Submitted That Met QC Criteria: August 8, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Membrane Transport Modulators; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Chloride Channel Agonists; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Ivacaftor
• Other Study ID Numbers: VX12-809-008