Clinical Trial Results:
A Phase 1, Randomized, Open-label Study to Evaluate the Relative Bioavailability, Food Effect, and Dose Proportionality of a Granule Formulation of Lumacaftor in Combination With Ivacaftor in Healthy Adult Subjects
Summary
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EudraCT number |
2019-002254-23 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
01 Dec 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Oct 2019
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First version publication date |
04 Oct 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
VX15-809-014
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Vertex Pharmaceuticals Incorporated
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Sponsor organisation address |
50 Northern Avenue, Boston, Massachusetts, United States,
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Public contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617 341 6777, medicalinfo@vrtx.com
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Scientific contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617 341 6777, medicalinfo@vrtx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001582-PIP01-13 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Feb 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Nov 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Dec 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the relative bioavailability of the granule formulation compared to the tablet formulation of lumacaftor (LUM)/ivacaftor (IVA)
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Protection of trial subjects |
The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Council on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Sep 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
16
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
16
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
Pre-assignment
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Screening details |
A total of 16 subjects were enrolled and randomized in the study. | |||||||||||||||
Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence 1 | |||||||||||||||
Arm description |
Subjects received LUM/IVA Dose 1 tablet formulation in fed state in treatment period 1, then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 2, then LUM/IVA Dose 1 granule formulation in fed state in treatment period 3, and then LUM/IVA Dose 2 granule formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
LUM/IVA
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Investigational medicinal product code |
VX-809/ VX-770
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Other name |
Lumacaftor/Ivacaftor fixed dose combination
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Pharmaceutical forms |
Tablet, Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of LUM/IVA tablet or granule formulation in the fed or fasted state on Day 1 in treatment period 1, 2, 3 and 4 as per the sequence.
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Arm title
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Sequence 2 | |||||||||||||||
Arm description |
Subjects received LUM/IVA Dose 1 granule formulation in fed state in treatment period 1, then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 2, then LUM/IVA Dose 2 granule formulation in fed state in treatment period 3, and then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
LUM/IVA
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Investigational medicinal product code |
VX-809/ VX-770
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Other name |
Lumacaftor/Ivacaftor fixed dose combination
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Pharmaceutical forms |
Granules, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of LUM/IVA tablet or granule formulation in the fed or fasted state on Day 1 in treatment period 1, 2, 3 and 4 as per the sequence.
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Arm title
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Sequence 3 | |||||||||||||||
Arm description |
Subjects received LUM/IVA Dose 2 granule formulation in fed state in treatment period 1, then LUM/IVA Dose 1 granule formulation in fed state in treatment period 2, then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 3, and then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
LUM/IVA
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Investigational medicinal product code |
VX-809/ VX-770
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Other name |
Lumacaftor/Ivacaftor fixed dose combination
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Pharmaceutical forms |
Granules, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of LUM/IVA tablet or granule formulation in the fed or fasted state on Day 1 in treatment period 1, 2, 3 and 4 as per the sequence.
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Arm title
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Sequence 4 | |||||||||||||||
Arm description |
Subjects received LUM/IVA Dose 1 granule formulation in fasted state in treatment period 1, then LUM/IVA Dose 2 granule formulation in fed state in treatment period 2, then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 3, and then LUM/IVA Dose 1 granule formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
LUM/IVA
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Investigational medicinal product code |
VX-809/ VX-770
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Other name |
Lumacaftor/Ivacaftor fixed dose combination
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Pharmaceutical forms |
Granules, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of LUM/IVA tablet or granule formulation in the fed or fasted state on Day 1 in treatment period 1, 2, 3 and 4 as per the sequence.
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Baseline characteristics reporting groups
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Reporting group title |
Sequence 1
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Reporting group description |
Subjects received LUM/IVA Dose 1 tablet formulation in fed state in treatment period 1, then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 2, then LUM/IVA Dose 1 granule formulation in fed state in treatment period 3, and then LUM/IVA Dose 2 granule formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence 2
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Reporting group description |
Subjects received LUM/IVA Dose 1 granule formulation in fed state in treatment period 1, then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 2, then LUM/IVA Dose 2 granule formulation in fed state in treatment period 3, and then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence 3
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Reporting group description |
Subjects received LUM/IVA Dose 2 granule formulation in fed state in treatment period 1, then LUM/IVA Dose 1 granule formulation in fed state in treatment period 2, then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 3, and then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence 4
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Reporting group description |
Subjects received LUM/IVA Dose 1 granule formulation in fasted state in treatment period 1, then LUM/IVA Dose 2 granule formulation in fed state in treatment period 2, then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 3, and then LUM/IVA Dose 1 granule formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sequence 1
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Reporting group description |
Subjects received LUM/IVA Dose 1 tablet formulation in fed state in treatment period 1, then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 2, then LUM/IVA Dose 1 granule formulation in fed state in treatment period 3, and then LUM/IVA Dose 2 granule formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||
Reporting group title |
Sequence 2
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Reporting group description |
Subjects received LUM/IVA Dose 1 granule formulation in fed state in treatment period 1, then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 2, then LUM/IVA Dose 2 granule formulation in fed state in treatment period 3, and then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||
Reporting group title |
Sequence 3
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Reporting group description |
Subjects received LUM/IVA Dose 2 granule formulation in fed state in treatment period 1, then LUM/IVA Dose 1 granule formulation in fed state in treatment period 2, then LUM/IVA Dose 1 granule formulation in fasted state in treatment period 3, and then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||
Reporting group title |
Sequence 4
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Reporting group description |
Subjects received LUM/IVA Dose 1 granule formulation in fasted state in treatment period 1, then LUM/IVA Dose 2 granule formulation in fed state in treatment period 2, then LUM/IVA Dose 1 tablet formulation in fed state in treatment period 3, and then LUM/IVA Dose 1 granule formulation in fed state in treatment period 4. A washout period of at least 10 days occurred between each dosing occasion. | ||
Subject analysis set title |
Treatment A: LUM/IVA Dose 1 Tablet (Fed)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received LUM/IVA Dose 1 tablet formulation in fed state.
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Subject analysis set title |
Treatment B: LUM/IVA Dose 1 Granule (Fasted)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All Subjects who received LUM/IVA Dose 1 granule formulation in fasted state.
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Subject analysis set title |
Treatment B: LUM/IVA Dose 1 Granule (Fed)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All Subjects who received LUM/IVA Dose 1 granule formulation in fed state.
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Subject analysis set title |
Treatment C: LUM/IVA Dose 2 Granule (Fed)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All Subjects who received LUM/IVA Dose 2 granule formulation in fed state.
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End point title |
Maximum Observed Plasma Concentration (Cmax) of LUM and IVA [1] | ||||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 up to Day 6 for each treatment period
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned. No statistical comparisons were planned for the primary pharmacokinetic (PK) endpoint. PK set included participants who received at least 1 dose of study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here “Number Analyzed” signifies those participants who were evaluable for this outcome measure in the specified treatment period. |
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No statistical analyses for this end point |
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End point title |
Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity [AUC(0 - inf)] of LUM and IVA [2] | ||||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 up to Day 6 for each treatment period
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned. No statistical comparisons were planned for the primary PK endpoint. PK set included participants who received at least 1 dose of study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here “Number Analyzed” signifies those participants who were evaluable for this outcome measure in the specified treatment period. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug up to 10 days after last dose of study drug in treatment period 4
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Treatment A: LUM/IVA Dose 1 Tablet (Fed)
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Reporting group description |
All subjects who received LUM/IVA Dose 1 tablet formulation in fed state. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment B: LUM/IVA Dose 1 Granule (Fasted)
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Reporting group description |
All Subjects who received LUM/IVA Dose 1 granule formulation in fasted state. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment B: LUM/IVA Dose 1 Granule (Fed)
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Reporting group description |
All Subjects who received LUM/IVA Dose 1 granule formulation in fed state. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment C: LUM/IVA Dose 2 Granule (Fed)
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Reporting group description |
All Subjects who received LUM/IVA Dose 2 granule formulation in fed state. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |