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Phase 1, QT/QTC Interval Study in Healthy Subjects

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Lumacaftor
Lumacaftor Placebo
Ivacaftor
Ivacaftor Placebo
moxifloxacin hydrochloride
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A

Part B

Arm 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

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

Outcomes

Primary Outcome Measures

(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
(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

Secondary Outcome Measures

(Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC
(Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin
(Part B) Time-matched, baseline-adjusted non-QT interval parameters obtained from a continuous ECG recording over a 24-hour interval
(Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC
(Part B) PK/PD relationship between plasma concentration and QT/QTc interval
(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

Full Information

First Posted
July 19, 2013
Last Updated
August 8, 2014
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT01910415
Brief Title
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

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A
Arm Type
Experimental
Arm 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
Arm Title
Part B
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Lumacaftor
Other Intervention Name(s)
VX-809
Intervention Type
Drug
Intervention Name(s)
Lumacaftor Placebo
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
VX-770
Intervention Type
Drug
Intervention Name(s)
Ivacaftor Placebo
Intervention Type
Drug
Intervention Name(s)
moxifloxacin hydrochloride
Primary Outcome Measure Information:
Title
(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
Title
(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
Secondary Outcome Measure Information:
Title
(Part A) PK parameters of lumacaftor and M28-lumacaftor in plasma including Cmax and AUC
Time Frame
up to 11 days
Title
(Part B) Time-matched, baseline-adjusted QTcF intervals obtained after a single 400-mg dose of moxifloxacin
Time Frame
up to 14 days
Title
(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
Title
(Part B) PK parameters of lumacaftor, M28-lumacaftor, ivacaftor, M1-ivacaftor, and M6-ivacaftor including Cmax and AUC
Time Frame
up to 15 days
Title
(Part B) PK/PD relationship between plasma concentration and QT/QTc interval
Time Frame
up to 14 days
Title
(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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
City
Zuidlaren
Country
Netherlands

12. IPD Sharing Statement

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Phase 1, QT/QTC Interval Study in Healthy Subjects

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