Clinical trial NCT01910415: Phase 1, QT/QTC Interval Study in Healthy Subjects
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2013-07-29
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: (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
timeFrame: 7 days
measure: (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
timeFrame: 7 days
Secondary outcomes:
measure: (Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC
timeFrame: up to 11 days
measure: (Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin
timeFrame: up to 14 days
measure: (Part B) Time-matched, baseline-adjusted non-QT interval parameters obtained from a continuous ECG recording over a 24-hour interval
timeFrame: up to 14 days
measure: (Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC
timeFrame: up to 15 days
measure: (Part B) PK/PD relationship between plasma concentration and QT/QTc interval
timeFrame: up to 14 days
measure: (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
timeFrame: up to 24 days
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
Study officials:
References: