Phase 1, QT/QTC Interval Study in Healthy Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01910415
• Date of registration: 19/07/2013
• Prospective Registration: No
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: Phase 1, QT/QTC Interval Study in Healthy Subjects
• Scientific title: 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
• Date of first enrolment: June 2013
• Target sample size: 200
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01910415
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: moxifloxacin hydrochloride

Drug: Lumacaftor

Drug: Lumacaftor Placebo

Drug: Ivacaftor

Drug: Ivacaftor Placebo

Primary Outcome(s)

(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 [Time Frame: 7 days]

(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 [Time Frame: 7 days]

Secondary Outcome(s)

(Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC [Time Frame: up to 11 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 [Time Frame: up to 24 days]

(Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC [Time Frame: up to 15 days]

(Part B) Time-matched, baseline-adjusted non-QT interval parameters obtained from a continuous ECG recording over a 24-hour interval [Time Frame: up to 14 days]

(Part B) PK/PD relationship between plasma concentration and QT/QTc interval [Time Frame: up to 14 days]

(Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin [Time Frame: up to 14 days]

Secondary ID(s)

VX12-809-008

Source(s) of Monetary Support

Please refer to primary and secondary sponsors