Phase 1, QT/QTC Interval Study in Healthy Subjects

NCT01910415 | Completed Phase 1

• 1 other identifier: VX12-809-008
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• (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 Outcomes (6)

• (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

Study Arms (2)

Part A

EXPERIMENTAL

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; Drug: Lumacaftor Placebo

Part B

EXPERIMENTAL

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

Interventions

Lumacaftor DRUG

Also known as: VX-809

Part A; Part B

Lumacaftor Placebo DRUG

Part A; Part B

Ivacaftor DRUG

Also known as: VX-770

Part B

Ivacaftor Placebo DRUG

Part B

moxifloxacin hydrochloride DRUG

Part B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (1)

Unknown Facility

Zuidlaren, Netherlands

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lumacaftor; ivacaftor; Moxifloxacin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2013
• First Posted: July 29, 2013
• Study Start: June 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: August 11, 2014

Record last verified: 2014-02

Locations

NL (1)