Trial Outcomes & Findings for Evaluation of VX-659/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age (NCT NCT03633526)
NCT ID: NCT03633526
Last Updated: 2020-02-05
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
18 participants
Primary outcome timeframe
Day 1 and Day 15
Results posted on
2020-02-05
Participant Flow
A total of 18 participants were enrolled in this study. Two participants were enrolled but were not dosed in triple combination (TC) treatment period. Therefore, results are reported for 16 participants.
This study was conducted in participants with cystic fibrosis (CF) 6-11 years of age. The study was terminated before start of Part B at Sponsor's discretion.
Participant milestones
| Measure |
VX-659/TEZ/IVA
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Overall Study
STARTED
|
16
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of VX-659/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age
Baseline characteristics by cohort
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Age, Continuous
|
9.2 years
STANDARD_DEVIATION 1.4 • n=93 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 15Population: Pharmacokinetic (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 subjects who were evaluable at the specified timepoint.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA
IVA: Day 15
|
0.733 microgram per milliliter (mcg/mL)
Standard Deviation 0.256
|
|
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA
VX-659: Day 1
|
1.81 microgram per milliliter (mcg/mL)
Standard Deviation 0.858
|
|
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA
VX-659: Day 15
|
2.55 microgram per milliliter (mcg/mL)
Standard Deviation 1.21
|
|
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA
TEZ: Day 1
|
4.53 microgram per milliliter (mcg/mL)
Standard Deviation 1.65
|
|
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA
TEZ: Day 15
|
5.22 microgram per milliliter (mcg/mL)
Standard Deviation 1.69
|
|
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA
IVA: Day 1
|
0.536 microgram per milliliter (mcg/mL)
Standard Deviation 0.208
|
PRIMARY outcome
Timeframe: Day 8 and Day 15Population: PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA
VX-659: Day 8
|
0.358 mcg/mL
Standard Deviation 0.259
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA
VX-659: Day 15
|
0.367 mcg/mL
Standard Deviation 0.283
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA
TEZ: Day 8
|
0.897 mcg/mL
Standard Deviation 0.488
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA
TEZ: Day 15
|
0.740 mcg/mL
Standard Deviation 0.421
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA
IVA: Day 8
|
0.289 mcg/mL
Standard Deviation 0.195
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA
IVA: Day 15
|
0.283 mcg/mL
Standard Deviation 0.241
|
PRIMARY outcome
Timeframe: Day 1 and Day 15Population: PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA
VX-659: Day 1
|
5.41 hour*mcg/mL (h*mcg/mL)
Standard Deviation 3.65
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA
VX-659: Day 15
|
8.55 hour*mcg/mL (h*mcg/mL)
Standard Deviation 4.50
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA
TEZ: Day 1
|
15.5 hour*mcg/mL (h*mcg/mL)
Standard Deviation 5.36
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA
TEZ: Day 15
|
19.3 hour*mcg/mL (h*mcg/mL)
Standard Deviation 7.26
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA
IVA: Day 1
|
1.64 hour*mcg/mL (h*mcg/mL)
Standard Deviation 0.795
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA
IVA: Day 15
|
2.95 hour*mcg/mL (h*mcg/mL)
Standard Deviation 1.18
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK set. Here "Number analyzed" signifies those subjects who were evaluable at the specified timepoint.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-TEZ: Day 1
|
1.63 mcg/mL
Standard Deviation 0.553
|
|
Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-TEZ: Day 15
|
5.04 mcg/mL
Standard Deviation 1.27
|
|
Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-IVA: Day 1
|
1.25 mcg/mL
Standard Deviation 0.449
|
|
Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-IVA: Day 15
|
1.73 mcg/mL
Standard Deviation 0.741
|
SECONDARY outcome
Timeframe: Day 8 and Day 15Population: PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-TEZ: Day 8
|
3.56 mcg/mL
Standard Deviation 1.33
|
|
Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-TEZ: Day 15
|
3.35 mcg/mL
Standard Deviation 1.23
|
|
Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-IVA: Day 8
|
0.816 mcg/mL
Standard Deviation 0.491
|
|
Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-IVA: Day 15
|
0.858 mcg/mL
Standard Deviation 0.672
|
SECONDARY outcome
Timeframe: Day 1 and Day 15Population: PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-TEZ: Day 1
|
5.52 h*mcg/mL
Standard Deviation 2.87
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-TEZ: Day 15
|
25.2 h*mcg/mL
Standard Deviation 7.70
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-IVA: Day 1
|
3.60 h*mcg/mL
Standard Deviation 1.87
|
|
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
M1-IVA: Day 15
|
6.98 h*mcg/mL
Standard Deviation 2.94
|
SECONDARY outcome
Timeframe: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)Population: Safety set included all participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
VX-659/TEZ/IVA
n=16 Participants
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
13 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
1 Participants
|
Adverse Events
VX-659/TEZ/IVA
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
VX-659/TEZ/IVA
n=16 participants at risk
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
Other adverse events
| Measure |
VX-659/TEZ/IVA
n=16 participants at risk
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
|
|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Gastrointestinal disorders
Post-tussive vomiting
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
2/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
General disorders
Chills
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
General disorders
Fatigue
|
18.8%
3/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
General disorders
Pyrexia
|
12.5%
2/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Injury, poisoning and procedural complications
Procedural anxiety
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Activated partial thromboplastin time prolonged
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Alanine aminotransferase increased
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Bacterial test positive
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Human rhinovirus test positive
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
International normalised ratio increased
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Prothrombin time prolonged
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Pulmonary function test decreased
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Investigations
Respirovirus test positive
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Nervous system disorders
Headache
|
37.5%
6/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
43.8%
7/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discharge discolouration
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
12.5%
2/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
12.5%
2/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Skin and subcutaneous tissue disorders
Rash vesicular
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
|
Vascular disorders
Hot flush
|
6.2%
1/16 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place