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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3b Open-label Study to Assess the Effect of Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor (IVA) on Glucose Tolerance in Cystic Fibrosis Subjects With Abnormal Glucose Metabolism

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: ELX/TEZ/IVA
* Drug: IVA


Participation Criteria
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Eligibility Criteria
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Key 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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELX/TEZ/IVA<br>Participants received ELX 200 mg /TEZ 100 mg /IVA 150 mg in the morning and IVA 150 mg in the evening. | Drug: ELX/TEZ/IVA<br>* Fixed dose combination (FDC) tablets for oral administration.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Tablets for oral administration.<br>* Other names: ivacaftor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2-hour Blood Glucose Levels Following an OGTT to the Average of Week 36 and Week 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. | Baseline, Week 36 and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Improvement in Dysglycemia Categorization at 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. | Baseline, Week 48 | 
| 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 |