Phase 1, QT/QTC Interval Study in Healthy Subjects

Vertex Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: Ivacaftor Placebo; Drug: moxifloxacin hydrochloride; Drug: Ivacaftor; Drug: Lumacaftor Placebo; Drug: Lumacaftor

Study type: Interventional

Funder types: Industry

Identifiers

NCT01910415

VX12-809-008

Details and patient eligibility

About

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.

Enrollment: 200 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

---

200 participants in 2 patient groups

Part A

Experimental group

Description:

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

Treatment:

Drug: Lumacaftor Placebo

Drug: Lumacaftor

Part B

Experimental group

Description:

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

Treatment:

Drug: Lumacaftor Placebo

Drug: Lumacaftor

Drug: Ivacaftor Placebo

Drug: Ivacaftor

Drug: moxifloxacin hydrochloride