Trial Outcomes & Findings for A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF) (NCT NCT03150719)
NCT ID: NCT03150719
Last Updated: 2019-09-12
Results Overview
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
98 participants
Primary outcome timeframe
Day 1 up to Day 84
Results posted on
2019-09-12
Participant Flow
A total of 98 participants were randomized: 47 in placebo group and 51 in tezacaftor (TEZ)/ivacaftor (IVA) group. One participant in TEZ/IVA group did not receive any study drug.
Participant milestones
| Measure |
Placebo
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
50
|
|
Overall Study
COMPLETED
|
46
|
48
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
Baseline characteristics by cohort
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
Total
n=97 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33.3 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
34.3 years
STANDARD_DEVIATION 8.7 • n=7 Participants
|
33.8 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to Day 84Population: Safety set included all participants who received at least 1 dose of study drug.
RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
|
10 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 28 and Day 56Population: Full analysis set (FAS) included all randomized participants who carried the intended cystic fibrosis transmembrane conductance regulator gene (CFTR) allele mutation and had received at least 1 dose of study drug.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Day 28 and Day 56 Measurements
|
-0.6 percent predicted of FEV1
Standard Deviation 3.4
|
2.2 percent predicted of FEV1
Standard Deviation 4.8
|
SECONDARY outcome
Timeframe: Baseline, Day 28 and Day 56Population: FAS.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Relative Change From Baseline in ppFEV1 at Average of Day 28 and Day 56 Measurements
|
-1.5 percent change
Standard Deviation 8.1
|
5.2 percent change
Standard Deviation 12.0
|
SECONDARY outcome
Timeframe: Baseline, Day 28 and Day 56Population: FAS.
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Day 28 and Day 56 Measurements
|
4.7 units on a scale
Standard Deviation 15.4
|
5.7 units on a scale
Standard Deviation 14.2
|
SECONDARY outcome
Timeframe: Day 1 through Day 56Population: Safety set.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Tolerability as Assessed by Number of Participants Who Discontinued Treatment
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 84Population: Safety set.
Outcome measures
| Measure |
Placebo
n=47 Participants
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 Participants
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
39 Participants
|
37 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
9 Participants
|
5 Participants
|
Adverse Events
Placebo
Serious events: 9 serious events
Other events: 28 other events
Deaths: 0 deaths
TEZ/IVA
Serious events: 5 serious events
Other events: 30 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Placebo
n=47 participants at risk
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 participants at risk
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
14.9%
7/47 • Day 1 up to Day 84
|
6.0%
3/50 • Day 1 up to Day 84
|
|
Infections and infestations
Sepsis
|
0.00%
0/47 • Day 1 up to Day 84
|
2.0%
1/50 • Day 1 up to Day 84
|
|
Infections and infestations
Lower respiratory tract infection
|
2.1%
1/47 • Day 1 up to Day 84
|
0.00%
0/50 • Day 1 up to Day 84
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/47 • Day 1 up to Day 84
|
2.0%
1/50 • Day 1 up to Day 84
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.00%
0/47 • Day 1 up to Day 84
|
2.0%
1/50 • Day 1 up to Day 84
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/47 • Day 1 up to Day 84
|
2.0%
1/50 • Day 1 up to Day 84
|
|
Cardiac disorders
Pericardial effusion
|
2.1%
1/47 • Day 1 up to Day 84
|
0.00%
0/50 • Day 1 up to Day 84
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.1%
1/47 • Day 1 up to Day 84
|
0.00%
0/50 • Day 1 up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
2.1%
1/47 • Day 1 up to Day 84
|
0.00%
0/50 • Day 1 up to Day 84
|
Other adverse events
| Measure |
Placebo
n=47 participants at risk
Participants received placebo matched to TEZ/IVA fixed-dose combination tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 56 days.
|
TEZ/IVA
n=50 participants at risk
Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 56 days.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.0%
8/47 • Day 1 up to Day 84
|
18.0%
9/50 • Day 1 up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.6%
5/47 • Day 1 up to Day 84
|
10.0%
5/50 • Day 1 up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
4.3%
2/47 • Day 1 up to Day 84
|
6.0%
3/50 • Day 1 up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Respiration abnormal
|
2.1%
1/47 • Day 1 up to Day 84
|
6.0%
3/50 • Day 1 up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.4%
3/47 • Day 1 up to Day 84
|
4.0%
2/50 • Day 1 up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
10.6%
5/47 • Day 1 up to Day 84
|
4.0%
2/50 • Day 1 up to Day 84
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.6%
5/47 • Day 1 up to Day 84
|
8.0%
4/50 • Day 1 up to Day 84
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/47 • Day 1 up to Day 84
|
8.0%
4/50 • Day 1 up to Day 84
|
|
Gastrointestinal disorders
Nausea
|
4.3%
2/47 • Day 1 up to Day 84
|
8.0%
4/50 • Day 1 up to Day 84
|
|
Gastrointestinal disorders
Diarrhoea
|
6.4%
3/47 • Day 1 up to Day 84
|
2.0%
1/50 • Day 1 up to Day 84
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/47 • Day 1 up to Day 84
|
12.0%
6/50 • Day 1 up to Day 84
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
19.1%
9/47 • Day 1 up to Day 84
|
8.0%
4/50 • Day 1 up to Day 84
|
|
Nervous system disorders
Headache
|
14.9%
7/47 • Day 1 up to Day 84
|
12.0%
6/50 • Day 1 up to Day 84
|
|
Investigations
Bacterial test positive
|
0.00%
0/47 • Day 1 up to Day 84
|
6.0%
3/50 • Day 1 up to Day 84
|
|
General disorders
Fatigue
|
8.5%
4/47 • Day 1 up to Day 84
|
4.0%
2/50 • Day 1 up to Day 84
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.4%
3/47 • Day 1 up to Day 84
|
2.0%
1/50 • Day 1 up to Day 84
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER