Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Placebo-matched-to-ivacaftor tablet; Drug: Ivacaftor

Study type: Interventional

Funder types: Industry

Identifiers

NCT01685801

VX12-770-113

Details and patient eligibility

About

This study is a multiple within participant crossover study to evaluate the effect of ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator (CFTR) function.

Full description

CFTR Mutations associated with residual function or defective messenger ribonucleic acid (mRNA) splicing include the following:

R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A, 1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C, 405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C, 621+3A->G, 621+1G->T.

Enrollment: 24 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participants with confirmed diagnosis of CF
• Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing
• FEV1 >= 40 percent (%)
• 12 years of age or older
• Willing to agree to meet the contraception requirements
• Able to swallow tablets

Exclusion criteria

• A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D
• Unable to perform spirometry
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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24 participants in 4 patient groups

Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)

Experimental group

Description:

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Treatment:

Drug: Placebo-matched-to-ivacaftor tablet

Drug: Ivacaftor

Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)

Experimental group

Description:

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Treatment:

Drug: Placebo-matched-to-ivacaftor tablet

Drug: Ivacaftor

Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)

Experimental group

Description:

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Treatment:

Drug: Placebo-matched-to-ivacaftor tablet

Drug: Ivacaftor

Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)

Experimental group

Description:

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Treatment:

Drug: Placebo-matched-to-ivacaftor tablet

Drug: Ivacaftor