A Study to Assess the Effect of ELX/TEZ/IVA on Glucose Tolerance in Participants With Cystic Fibrosis (CF)

Phase 3

Completed

Brief Summary: This study was evaluate the effect of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) on glucose tolerance in CF participants, 12 years of age and older who are heterozygous for the F508del mutation and a minimal function mutation (F/MF genotypes), with abnormal glucose metabolism.

Recruitment & Eligibility

Inclusion Criteria

Heterozygous for F508del and an MF mutation (F/MF genotypes)
Forced expiratory volume in 1 second (FEV1) value ≥ 30% of predicted mean for age, sex, and height
Abnormal glucose tolerance determined by an OGTT as either:
- Impaired glucose tolerance (IGT) defined as 2 hour post OGTT blood glucose level ≥140 to <200 mg/dL (≥7.77 to <11.10 mmol/L) and fasting blood glucose level <126 mg/dL (<7.00 mmol/L)
- CF-related diabetes (CFRD) defined as either fasting hyperglycemia (blood glucose level ≥126 mg/dL [≥7.00 mmol/L] after an 8-hour fast) or 2-hour post OGTT blood glucose level ≥200 mg/dL (≥11.10 mmol/L)

Key

Exclusion Criteria

Clinically significant liver cirrhosis with or without portal hypertension
Solid organ or hematological transplantation
Lung infection with organisms associated with a more rapid decline in pulmonary status
Type 1 or Type 2 diabetes
Duration of CFRD ≥5 years

Other protocol defined Inclusion/Exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
ELX/TEZ/IVA	IVA	Participants received ELX 200 mg /TEZ 100 mg /IVA 150 mg in the morning and IVA 150 mg in the evening.
ELX/TEZ/IVA	ELX/TEZ/IVA	Participants received ELX 200 mg /TEZ 100 mg /IVA 150 mg in the morning and IVA 150 mg in the evening.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in 2-hour Blood Glucose Levels Following an OGTT to the Average of Week 36 and Week 48	Baseline, Week 36 and 48	Baseline 2-hour post-OGTT blood glucose level was defined as the average of valid pre-dose measurements at screening and Day 1. OGTT results were considered valid only when the participant was fasting for at least 8 hours.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Improvement in Dysglycemia Categorization at Week 48	Baseline, Week 48	Baseline dysglycemia category was defined as the most recent non-missing measurement before the first dose of study drug in the treatment period. Improvement in dysglycemia is a change from cystic fibrosis-related diabetes (CFRD) at baseline to impaired glucose tolerance (IGT)/normal glucose tolerance (NGT) at Week 48 OR change from IGT at baseline to NGT at Week 48. CFRD: 2-hour post-OGTT blood glucose level ≥200 mg/dL or fasting blood glucose level ≥126 mg/dL; IGT: 2-hour post-OGTT blood glucose level ≥140 to \<200 mg/dL and fasting blood glucose level \<126 mg/dL; NGT: 2 hour post-OGTT blood glucose level \<140 mg/dL and fasting blood glucose level \<126 mg/dL.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 52

Locations (41): Royal Adelaide Hospital
🇦🇺
Adelaide, Australia
The Prince Charles Hospital
🇦🇺
Chermside, Australia
Alfred Hospital
🇦🇺
Melbourne, Australia
Telethon Kids Institute
🇦🇺
Nedlands, Australia
The Royal Children's Hospital
🇦🇺
Parkville, VIC, Australia
Sydney Children's Hospital
🇦🇺
Randwick, Australia
Mater Adult Hospital
🇦🇺
South Brisbane, Australia
Queensland Children's Hospital
🇦🇺
South Brisbane, Australia
Westmead Hospital
🇦🇺
Westmead, Australia
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪
Brussels, Belgium
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Royal Adelaide Hospital
🇦🇺Adelaide, Australia