Trial Outcomes & Findings for Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease (NCT NCT02390219)

Last Updated: 2017-12-06

Results Overview

AE: any untoward medical occurrence in a participant during the study; event does not necessarily have a causal relationship with treatment. This includes any newly occurring event/previous condition that has increased in severity/frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs: AEs that started/ worsened on/after the start of study drug through the Safety Follow up Visit (4 weeks after the last dose of study drug). Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

46 participants

Primary outcome timeframe

Day 1 up to Week 28

Results posted on

2017-12-06

Participant Flow

A total of 46 participants were enrolled and treated in the study.

Participant milestones

Participant milestones
Measure	LUM/IVA Participants received lumacaftor (LUM) 400 milligram (mg) in combination with ivacaftor (IVA) 250 mg as fixed-dose combination (FDC) tablet orally every 12 hours (q12h) for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Overall Study STARTED	46
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	LUM/IVA Participants received lumacaftor (LUM) 400 milligram (mg) in combination with ivacaftor (IVA) 250 mg as fixed-dose combination (FDC) tablet orally every 12 hours (q12h) for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Overall Study Death	1
Overall Study Physician Decision	1
Overall Study Adverse Event	6
Overall Study Withdrawal by Subject	1
Overall Study Lost to Follow-up	2
Overall Study Other	2

Baseline Characteristics

Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LUM/IVA n=46 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Age, Continuous	32.1 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to Week 28

Population: Safety Set included all participants who were exposed to any amount of study drug.

Outcome measures

Outcome measures
Measure	LUM/IVA n=46 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Participants with AEs	43 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Participants with SAEs	18 Participants

SECONDARY outcome

Timeframe: Baseline, Up to Week 24

Population: Full Analysis Set (FAS) included all participants who were enrolled and administered any amount of study drug. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Outcome measures

Outcome measures
Measure	LUM/IVA n=32 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24	-0.4 Percent predicted of FEV1 Standard Error 0.7

SECONDARY outcome

Timeframe: Baseline, Up to Week 24

Population: FAS included all participants who were enrolled and administered any amount of study drug. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Outcome measures

Outcome measures
Measure	LUM/IVA n=32 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24	-0.02 Liter (L) Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline through Week 24

The duration for which participants received IV antibiotics for sinopulmonary signs and symptoms were reported. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Outcome measures

Outcome measures
Measure	LUM/IVA n=22 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Duration For Which Participants Received Intravenous (IV) Antibiotics	11.38 Days Standard Deviation 18.15

SECONDARY outcome

Timeframe: Baseline through Week 24

Number of hospitalizations (all causes) through Week 24 was summarized. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Outcome measures

Outcome measures
Measure	LUM/IVA n=16 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Number of Hospitalizations	23 Hospitalizations

SECONDARY outcome

Timeframe: Baseline, Day 15 and Week 4

Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. The average absolute change from baseline in sweat chloride was derived as: (Average of Day 15 and Week 4 value) minus Baseline value. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Outcome measures

Outcome measures
Measure	LUM/IVA n=41 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Absolute Change From Baseline in Sweat Chloride at Average of Day 15 and Week 4	-16.4 Millimoles per litre (mmol/L) Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, Through Week 24

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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Outcome measures

Outcome measures
Measure	LUM/IVA n=44 Participants Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score Through Week 24	2.5 Units on a scale Standard Error 1.7

Adverse Events

LUM/IVA

Serious events: 18 serious events

Other events: 43 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	LUM/IVA n=46 participants at risk Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Respiratory, thoracic and mediastinal disorders Cough	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Respiration abnormal	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Nervous system disorders Neuralgia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
General disorders Pyrexia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	34.8% 16/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Bacteraemia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Influenza	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Pneumonia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Other adverse events

Other adverse events
Measure	LUM/IVA n=46 participants at risk Participants received LUM 400 mg in combination with IVA 250 mg as FDC tablet orally q12h for 24 weeks. A reduced initial dose of LUM 200 mg in combination with IVA 125 mg FDC tablet orally q12h was permitted.
Vascular disorders Hot flush	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Vascular disorders Hypertension	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Immune system disorders Seasonal allergy	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Immune system disorders Drug hypersensitivity	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
General disorders Fatigue	15.2% 7/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
General disorders Chest pain	8.7% 4/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
General disorders Pain	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
General disorders Pyrexia	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
General disorders Asthenia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Psychiatric disorders Insomnia	8.7% 4/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Psychiatric disorders Affect lability	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Psychiatric disorders Anxiety	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Psychiatric disorders Depression	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Psychiatric disorders Irritability	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Reproductive system and breast disorders Breast pain	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Reproductive system and breast disorders Menorrhagia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Alanine aminotransferase increased	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Aspartate aminotransferase increased	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Pulmonary function test decreased	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Blood glucose increased	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Gamma-glutamyltransferase increased	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Blood creatine phosphokinase increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Blood glucose decreased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Blood immunoglobulin E increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Blood phosphorus decreased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Blood pressure diastolic increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Forced expiratory volume decreased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Fungal test positive	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Oxygen consumption increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Prostatic specific antigen increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Sputum abnormal	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Weight decreased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations Weight increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Investigations White blood cell count increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Cardiac disorders Palpitations	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Cardiac disorders Tachycardia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Respiration abnormal	54.3% 25/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Cough	45.7% 21/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Dyspnoea	43.5% 20/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Sputum increased	28.3% 13/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	19.6% 9/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Haemoptysis	15.2% 7/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.9% 5/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Wheezing	10.9% 5/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Productive cough	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Asthma	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Increased viscosity of bronchial secretion	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Lower respiratory tract congestion	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Painful respiration	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Sinus congestion	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Sputum retention	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Nervous system disorders Headache	15.2% 7/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Nervous system disorders Lethargy	8.7% 4/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Nervous system disorders Dizziness	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Nervous system disorders Transient ischaemic attack	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Eye disorders Lacrimation increased	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Ear and labyrinth disorders Vertigo	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Diarrhoea	10.9% 5/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Nausea	10.9% 5/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Abdominal pain	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Abdominal pain upper	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Constipation	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Flatulence	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Abdominal discomfort	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Dyspepsia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Dysphagia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Gastrointestinal tract mucosal discolouration	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Toothache	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Gastrointestinal disorders Vomiting	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Renal and urinary disorders Nephrocalcinosis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Rash	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Pruritus	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Acne	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Alopecia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Eczema	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Night sweats	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Rash macular	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Skin and subcutaneous tissue disorders Urticaria	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Back pain	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Muscle spasms	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Musculoskeletal and connective tissue disorders Myalgia	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Metabolism and nutrition disorders Decreased appetite	10.9% 5/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Metabolism and nutrition disorders Dehydration	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	43.5% 20/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Nasopharyngitis	6.5% 3/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Gastroenteritis viral	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Vulvovaginal mycotic infection	4.3% 2/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Chronic sinusitis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Clostridium difficile colitis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Clostridium difficile infection	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Conjunctivitis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Influenza	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Labyrinthitis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Oral candidiasis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Sinusitis	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Sinusitis bacterial	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Tooth abscess	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Infections and infestations Upper respiratory tract infection	2.2% 1/46 • Day 1 up to Week 28 AEs were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Restriction Description: PI is free to publish results of the study after (1)first multi-center publication, (2)if 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