Safety, Tolerability, and Pharmacokinetics (PK) of CTP-499

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of CTP-499 following single dose administration.

Detailed Description
-----------------
This is a double-blind, single ascending dose administration study of four doses of CTP-499. Following dosing safety and tolerability will be assessed. Blood and urine samples will be taken for pharmacokinetics (PK) and bioavailability. Safety assessments will include monitoring of adverse events, vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, 12-lead ECGs, and physical examination findings. The plasma concentration time data for CTP-499 and its metabolites will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analysis. The primary pharmacokinetics parameters are: Cmax, Tmax, T1/2, AUClast and AUCinf for plasma; relative bioavailability; and Ae and CLr for urine.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Single-ascending-dose, Safety, Tolerability, Pharmacokinetics, and Relative Bioavailability Study of CTP-499 in Healthy Adults

Conditions
-----------------
Diabetic Nephropathy

Intervention / Treatment
-----------------
* Drug: CTP-499
* Drug: CTP-499


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy volunteers ages 18 to 55 years old nonsmokers BMI of 18 to 30 kg/m2 Exclusion Criteria: Significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders of drug hypersensitivity Systolic Blood pressure < 90 or > 140, diastolic bp > 90

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part A<br>Single ascending dose administration of four doses of CTP-499 as tablets under fasting condition. 8 subjects per dose group will be enrolled with a 3:1 randomization of active drug to placebo. Dose levels: 600mg -> 1200mg -> 1800mg -> 2400mg | Drug: CTP-499<br>* 600 mg, 1200 mg, 1800 mg and 2400 mg<br>|
| Active Comparator: Part B<br>Part B will consist of a single 400 mg dose of an immediate release capsule of CTP-499 administered under fasting conditions. In Part B 6 subjects will be enrolled. | Drug: CTP-499<br>* 400 mg immediate release capsule<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability of CTP-499 | Assessments will include monitoring of adverse events, vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, 12 lead ECGs, and physical examination findings. Safety data will be summarized using descriptive statistics for all subjects who receive at least 1 dose. Adverse events will be summarized by frequency. Abnormal laboratory and physical exam findings will be summarized by dose and treatment. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess Pharmacokinetics, Pharmacodynamics and relative bioavailability | Pharmacokinetics: individual and mean concentration time profiles will be presented graphically. Alll PK parameters will be summarized by dose group using descriptive statistics (eg n, arithmetic mean, SD, geometric mean, median, CV). Relative bioavailability will be estimated using the geometric mean values of dose normalized AUC for each dose. Pharmacodynamics: From the 12 lead ECG data, VR, PR, QRS, QT, QTcF andd QTcB will be reported for each time point and summarized using descriptive statistics. Mean temporal profiles for 12 lead ECG and vital signs will be presented graphically. | 2 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Safety, Tolerability, Pharmacokinetics, Healthy volunteers