Trial Outcomes & Findings for Lumacaftor/Ivacaftor Combination Therapy in Subjects With CF Who Have an A455E CFTR Mutation (NCT NCT03061331)
NCT ID: NCT03061331
Last Updated: 2018-10-02
Results Overview
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Study Baseline, Through Week 8
Results posted on
2018-10-02
Participant Flow
A total of 20 subjects were enrolled in this cross-over study.
Participant milestones
| Measure |
Sequence 1: First LUM/IVA, Then Placebo
Participants received Lumacaftor (LUM) 400 milligram (mg)/Ivacaftor (IVA) 250 mg fixed dose combination tablet orally every 12 hours (q12h) for 8 weeks in treatment period 1 followed by placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period.
|
Sequence 2: First Placebo, Then LUM/IVA
Participants received placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 1 followed by LUM 400 mg/IVA 250 mg fixed dose combination tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period.
|
|---|---|---|
|
Treatment Period 1 (8 Weeks)
STARTED
|
10
|
10
|
|
Treatment Period 1 (8 Weeks)
COMPLETED
|
10
|
10
|
|
Treatment Period 1 (8 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Washout Period (8 Weeks)
STARTED
|
10
|
10
|
|
Washout Period (8 Weeks)
COMPLETED
|
8
|
9
|
|
Washout Period (8 Weeks)
NOT COMPLETED
|
2
|
1
|
|
Treatment Period 2 (8 Weeks)
STARTED
|
8
|
9
|
|
Treatment Period 2 (8 Weeks)
COMPLETED
|
8
|
9
|
|
Treatment Period 2 (8 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: First LUM/IVA, Then Placebo
Participants received Lumacaftor (LUM) 400 milligram (mg)/Ivacaftor (IVA) 250 mg fixed dose combination tablet orally every 12 hours (q12h) for 8 weeks in treatment period 1 followed by placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period.
|
Sequence 2: First Placebo, Then LUM/IVA
Participants received placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 1 followed by LUM 400 mg/IVA 250 mg fixed dose combination tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period.
|
|---|---|---|
|
Washout Period (8 Weeks)
Adverse Event
|
2
|
1
|
Baseline Characteristics
Lumacaftor/Ivacaftor Combination Therapy in Subjects With CF Who Have an A455E CFTR Mutation
Baseline characteristics by cohort
| Measure |
Sequence 1: First LUM/IVA, Then Placebo
n=10 Participants
Participants received LUM 400 mg/IVA 250 mg fixed dose combination tablet orally q12h for 8 weeks in treatment period 1 followed by placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period.
|
Sequence 2: First Placebo, Then LUM/IVA
n=10 Participants
Participants received placebo matched to LUM/IVA tablet orally q12h for 8 weeks in treatment period 1 followed by LUM 400 mg/IVA 250 mg fixed dose combination tablet orally q12h for 8 weeks in treatment period 2. Two treatment periods were separated by 8-week washout period.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.2 years
STANDARD_DEVIATION 15.1 • n=5 Participants
|
34.7 years
STANDARD_DEVIATION 11.8 • n=7 Participants
|
38.0 years
STANDARD_DEVIATION 13.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Study Baseline, Through Week 8Population: Full Analysis set included as all randomized participants who had at least 1 A455E mutation and received at least 1 dose of study drug. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
Placebo
n=18 Participants
Placebo matched to LUM/IVA q12h for 8 weeks in Treatment Period 1 or 2
|
LUM/IVA
n=18 Participants
LUM 400 mg/IVA 250 mg fixed dose combination q12h for 8 weeks in Treatment Period 1 or 2.
|
|---|---|---|
|
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8
|
2.6 Percentage of predicted FEV1
Interval 0.2 to 4.9
|
2.7 Percentage of predicted FEV1
Interval 0.3 to 5.0
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
LUM/IVA
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=18 participants at risk
Placebo matched to LUM/IVA q12h for 8 weeks in Treatment Period 1 or 2.
|
LUM/IVA
n=19 participants at risk
LUM 400 mg/IVA 250 mg fixed dose combination q12h for 8 weeks in Treatment Period 1 or 2.
|
|---|---|---|
|
Infections and infestations
Tooth infection
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Infections and infestations
Wound infection
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Vascular disorders
Hypertension
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
General disorders
Fatigue
|
11.1%
2/18 • Up to Week 28
|
15.8%
3/19 • Up to Week 28
|
|
General disorders
Exercise tolerance decreased
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
General disorders
Influenza like illness
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Reproductive system and breast disorders
Menopausal symptoms
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Injury, poisoning and procedural complications
Muscle strain
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Investigations
Blood pressure increased
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
16.7%
3/18 • Up to Week 28
|
15.8%
3/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
3/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
3/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus discomfort
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.6%
1/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Respiration abnormal
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Sputum discoloured
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Nervous system disorders
Headache
|
0.00%
0/18 • Up to Week 28
|
21.1%
4/19 • Up to Week 28
|
|
Nervous system disorders
Dizziness
|
0.00%
0/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Nervous system disorders
Paraesthesia
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Ear and labyrinth disorders
Tinnitus
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/18 • Up to Week 28
|
42.1%
8/19 • Up to Week 28
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/18 • Up to Week 28
|
21.1%
4/19 • Up to Week 28
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/18 • Up to Week 28
|
21.1%
4/19 • Up to Week 28
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
3/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.6%
1/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Skin and subcutaneous tissue disorders
Acne
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Infections and infestations
Nasopharyngitis
|
11.1%
2/18 • Up to Week 28
|
15.8%
3/19 • Up to Week 28
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/18 • Up to Week 28
|
15.8%
3/19 • Up to Week 28
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
11.1%
2/18 • Up to Week 28
|
10.5%
2/19 • Up to Week 28
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Infections and infestations
Laryngitis
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/18 • Up to Week 28
|
5.3%
1/19 • Up to Week 28
|
|
Infections and infestations
Eye infection
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Infections and infestations
Impetigo
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
|
Infections and infestations
Sinusitis
|
5.6%
1/18 • Up to Week 28
|
0.00%
0/19 • Up to Week 28
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
- Publication restrictions are in place
Restriction type: OTHER