A Study of Safety, Tolerability, and Pharmacokinetics of Multiple-Ascending Doses of PHP-303 in Otherwise Healthy Overweight or Obese Subjects

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled multiple-ascending dose (MAD) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of PHP-303 in otherwise healthy overweight or obese volunteer subjects. Within each ascending dose cohort, subjects will be randomized in a 4:1 ratio to receive PHP-303 or placebo. The primary objective is to establish the safety and tolerability and maximum tolerated dose (MTD) of orally-administered PHP-303.

Official Title
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A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PHP-303 in Otherwise Healthy Overweight or Obese Subjects

Conditions
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Otherwise Healthy Overweight or Obese

Intervention / Treatment
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* Drug: PHP-303
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, ≥ 18 to ≤ 60 years of age. In good general health having no clinically significant diseases in medical history or evidence of clinically significant findings on physical examination, vital signs, laboratory results, and/or ECG at Screening, in the opinion of an Investigator. Willing to forego other forms of experimental treatment during the study. Exclusion Criteria: Any clinically significant condition that, in the opinion of an Investigator, could preclude the safe participation of the subject in the study or would prevent the subject from meeting the study requirements. Major surgery in the 6 months preceding Screening. Clinically-significant abnormal laboratory parameters. Positive urine drug test for alcohol, cotinine, and/or drugs of abuse (cocaine, tetrahydrocannabinol, amphetamines, methamphetamines, or benzodiazepines) at Screening or on admission to the study site. Electrocardiographic Fridericia's corrected QT interval (QTcF) interval > 450 msec for males and > 470 msec for females, or any other clinically significant electrocardiographic abnormality. Blood pressure results > 150 mmHg systolic or > 95 mmHg diastolic Female subject who is pregnant (positive pregnancy test at the Screening Visit or on admission to the study site), lactating, or planning to become pregnant during the study period or within 3 months after the final dose of study medication. History of drug or alcohol abuse or dependence within 1 year prior to Screening. History of cigarette smoking within 3 months of Screening. Known intolerance to lactose. Regular use of prescription drugs within 14 days of the first administration of study drug or non-prescription (over-the-counter) drugs within 7 days of the first administration of study drug or unwilling to abstain from prohibited medications through the end of study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>PHP-303, multiple oral dose, up to 5 ascending dose cohorts | Drug: PHP-303<br>* Investigational drug<br>|
| Placebo Comparator: Placebo<br>Placebo, multiple oral dose, up to 5 ascending dose cohorts | Other: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of multiple oral doses of PHP-303 - Incidence of Adverse Events | Assess the number of patients with adverse events | Up to 12 weeks | 
| Safety and tolerability of multiple oral doses of PHP-303 - number of patients with abnormal ECG | Number of patients with clinically significant change from baseline in standard 12 lead ECG parameters | Up to 12 weeks | 
| Safety and tolerability of multiple oral doses of PHP-303 - blood pressure | Number of patients with clinically significant change from baseline in systolic and diastolic blood pressure | Up to 12 weeks | 
| Safety and tolerability of multiple oral doses of PHP-303 - heart rate | Measured as number of heart beats per minute | Up to 12 weeks | 
| Safety and tolerability of multiple oral doses of PHP-303 - body temperature | Measurement of oral body temperature | Up to 12 weeks | 
| Safety and tolerability of multiple oral doses of PHP-303 - respiratory rate | Measured by number of breaths per minute | Up to 12 weeks | 
| Plasma concentration of multiple oral doses of PHP-303 - AUC | Area under the curve | Plasma Up to 12 weeks | 
| Plasma concentration of multiple oral doses of PHP-303 - Cmax | Maximum observed concentration | Up to 12 weeks | 
| Plasma concentration of multiple oral doses of PHP-303 - Tmax | Time to reach maximum measured plasma concentration | Up to 12 weeks | 
| Plasma concentration of multiple oral doses of PHP-303 - t1/2 | Determination of half-life | Up to 12 weeks |