Study to Evaluate Safety, Tolerability and PK of C-10355 and C-10358 in Healthy Subjects

Study Overview
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Brief Summary
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This two-part study will assess, in healthy volunteers, under both fasted and fed conditions, and in a sequential manner, the safety, tolerability and pharmacokinetics (PK) profile of single doses of C-10355 and C-10358 and single ascending doses of the selected compound compared to a single dose of Kalydeco®.

Official Title
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A Two-Part Open-Label, Randomized, Sequential, Crossover, Single Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of C-10355 and C-10358 in Healthy Volunteers, With a PK Comparison to Kalydeco®

Conditions
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Healthy

Intervention / Treatment
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* Drug: C-10355
* Drug: C-10358
* Drug: Kalydeco


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults between 18 and 50 years of age, inclusive Body weight ≥ 50 kg and BMI within the range of 18 to 30 kg/m2, inclusive, at screening Exclusion Criteria: History of clinically significant central nervous system (eg, seizures), cardiac, pulmonary, metabolic, renal (including nephrolithiasis), hepatic, including history of Gilbert's syndrome or gastrointestinal (GI) conditions PR interval ≥ 220 msec or QRS duration ≥ 120 msec or QTcF interval > 450 msec obtained at screening visit or prior to the first dose of study drug Liver function tests greater than the upper limit of normal. Positive blood screen for human immunodeficiency virus (HIV antibody), hepatitis B virus surface antigen, or hepatitis C virus antibody at screening Urinalysis positive for greater than trace blood, protein or glucose A positive screen for alcohol, drugs of abuse, or tobacco use. Inability to comply with food and beverage restrictions during study participation. Donation or blood collection or acute loss of blood prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C-10355, 25 mg<br>single oral dose. | Drug: C-10355<br> <br> |
| Active Comparator: C-10358, 25 mg<br>single oral dose. | Drug: C-10358<br> <br> |
| Active Comparator: C-10355 or C-10358, 75 mg<br>single oral dose. | Drug: C-10355<br> <br> Drug: C-10358<br> <br> |
| Active Comparator: C-10355 or C-10358, 150 mg<br>single oral dose. | Drug: C-10355<br> <br> Drug: C-10358<br> <br> |
| Active Comparator: Kalydeco, 150 mg<br>single oral dose. | Drug: Kalydeco<br> <br> |
| Active Comparator: C-10355 or C-10358, 300 mg<br>single oral dose. | Drug: C-10355<br> <br> Drug: C-10358<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | adverse events categorized by body system and MedDRA term | 24 hours | 
| Pharmacokinetic Profile | Measure exposure of test articles using area under the concentration time curve (AUC), maximum concentration (Cmax), half life (T 1/2) | 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subjects, Safety/Efficacy Study, Randomized, Open Label