Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Norketotifen in Healthy Subjects

Study Overview
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Brief Summary
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This is a Phase 1, single-center, double-blind, randomized, placebo-controlled, 2-part, single ascending dose and multiple dose cohort study of orally administered Norketotifen (NKT) in healthy subjects.

Detailed Description
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Single Ascending Dose: Three single ascending dose cohorts are planned. A total of 10 subjects will be enrolled in each cohort and will be randomly assigned to receive a single oral dose of NKT (n=8) or a matching placebo (n=2). A Safety Review Team (SRT) will review all available safety data in a blinded manner following the completion of each cohort to determine the next dose level to be evaluated in the next cohort. Multiple Dose Cohort: A total of 10 subjects will be enrolled and will be randomly assigned to receive multiple oral doses of NKT (n=8) or a matching placebo (n=2) once daily for an adequate number of days to reach steady state (the number of days will be determined based on the half-life of NKT in Part A). The dose of NKT to be evaluated will be determined by the SRT.

Official Title
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A Double-Blind, Placebo-Controlled, 2-Part, Single Ascending Dose and Multiple Dose Cohort Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Norketotifen in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Norketotifen Oral Capsule (Cohort 1)
* Drug: Norketotifen Oral Capsule (Cohort 2)
* Drug: Norketotifen Oral Capsule (Cohort 3)
* Drug: Norketotifen Oral Capsule (Multiple Dose Cohort)
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index (BMI) of 18 to 30 kg/m^2 Negative serum pregnancy test (females); females of childbearing potential and males must agree to use acceptable contraception Key Exclusion Criteria: Pregnant or lactating (females) Clinically significant past or current medical or surgical history Clinically significant illness or abnormality on physical examination, 12-lead ECG, laboratory values Participation in an investigational drug or device study within 30 days prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Norketotifen or Placebo (Cohort 1)<br> | Drug: Norketotifen Oral Capsule (Cohort 1)<br>* Single dose Norketotifen<br>Drug: Placebo Oral Capsule<br>* Placebo<br>|
| Experimental: Norketotifen or Placebo (Cohort 2)<br> | Drug: Norketotifen Oral Capsule (Cohort 2)<br>* Single dose Norketotifen<br>Drug: Placebo Oral Capsule<br>* Placebo<br>|
| Experimental: Norketotifen or Placebo (Cohort 3)<br> | Drug: Norketotifen Oral Capsule (Cohort 3)<br>* Single dose Norketotifen<br>Drug: Placebo Oral Capsule<br>* Placebo<br>|
| Experimental: Norketotifen or Placebo (Multiple Dose)<br> | Drug: Norketotifen Oral Capsule (Multiple Dose Cohort)<br>* Multiple dose Norketotifen<br>Drug: Placebo Oral Capsule<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events following single doses | Including clinically significant and Grade 3 abnormalities in laboratory values, vital signs, ECGs, and physical examination | Through Day 4 | 
| Number of subjects with adverse events following multiple doses | Including clinically significant and Grade 3 abnormalities in laboratory values, vital signs, ECGs, and physical examination | Through Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) following single doses |  | Through Day 4 | 
| Maximum plasma concentration (Cmax) following multiple doses |  | Through Day 7 | 
| Time to maximum concentration (Tmax) following single doses |  | Through Day 4 | 
| Time to maximum concentration (Tmax) following multiple doses |  | Through Day 7 | 
| Area under the plasma concentration time curve (AUC) following single doses |  | Through Day 4 | 
| Area under the plasma concentration time curve (AUC) following multiple doses |  | Through Day 7 | 
| Elimination half-life (t1/2) following single doses |  | Through Day 4 | 
| Elimination half-life (t1/2) following multiple doses |  | Through Day 7 | 
| Apparent clearance (CL/F) following single doses |  | Through Day 4 | 
| Apparent clearance (CL/F) following multiple doses |  | Through Day 7 | 
| Apparent volume of distribution (Vz/F) following single doses |  | Through Day 4 | 
| Apparent volume of distribution (Vz/F) following multiple doses |  | Through Day 7 |