A Phase 1 SAD and MAD Study of the Safety, Tolerability and PK of 7HP349 in Normal Healthy Male Subjects

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability and pharmacokinetics of 7HP349, an allosteric integrin activator, in healthy male subjects

Detailed Description
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This first-in-human (FIH) study consists of a placebo-controlled, sequential, dose escalation study to determine the safety, tolerability and pharmacokinetics (PK) of 7HP349 following single and multiple oral dose administration to healthy male subjects, with a separate, open-label food effect cohort at the optimal pharmacokinetic dose (OPD). The study will be carried out in 3 parts. Part A: This is a placebo-controlled, within-cohort randomized, double-blind, sequential, single ascending dose (SAD) escalation study to determine the safety, tolerability and PK of 7HP349 following administration of single oral doses in healthy male subjects, and to define the OPD of 7HP349. Part B: This is a placebo-controlled, within-cohort randomized, double-blind, sequential, multiple ascending dose (MAD) escalation study to determine the safety, tolerability and PK of 7HP349 following up to 5 once daily oral doses in healthy male subjects. Part C: This is a randomized, open label, two-treatment, three-period, crossover study to evaluate the effect of the fed or fasting prandial state on the single dose PK of 7HP349.

Official Title
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A Phase 1, Placebo-controlled, Within-Cohort Randomized, Double-blind, Single and Multiple Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of 7HP349 in Normal Healthy Male Subjects

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: 7HP349 Single Ascending Dose
* Drug: 7HP349 Multiple Ascending Dose
* Drug: Placebo Single Ascending Dose
* Drug: Placebo Multiple Ascending Dose
* Drug: 7HP349 Food Effect


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males between the ages of 18 and 45 years, inclusive Normal clinical chemistry, hepatic function, hematology, thyroid function Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 60 kg Agree to refrain from consuming products containing grapefruit, pomelo, star fruit or Seville oranges for at least 7 days before the first dose of study drug until the final discharge evaluation Positive immune status as defined in serum as measles, mumps, varicella-zoster viruses (VZR); Antibody Index (AI) ≥ 1.1, and positive Rubella: AI ≥ 1.0 Exclusion Criteria: Clinically significant history of disorders, infections or drug hypersensitivity as determined by the Investigator History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody Current treatment or treatment within 30 days with another investigational medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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
Interventional Model Description: This study consists of three parts, Part A, Part B and Part C, which will be undertaken sequentially. Part A is a SAD study to determine the safety, tolerability and PK of 7HP349 in healthy male subjects, and to define the OPD. Part B is a MAD study to determine the safety, tolerability and PK of 7HP349 following up to 5 once daily oral doses in healthy male subjects. Part C is a crossover study to evaluate the effect of the fed or fasting prandial state on the single dose PK of 7HP349.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 7HP349 Capsules<br>Part A: 7HP349 Capsules (5 cohorts); Part B: 7HP349 Capsules (2 cohorts); Part C: 7HP349 Capsules (3-period cross-over) | Drug: 7HP349 Single Ascending Dose<br>* Part A: 7HP349 Capsules, Single Ascending Dose (SAD)<br>* Other names: 7HP349 SAD;Drug: 7HP349 Multiple Ascending Dose<br>* Part B: 7HP349 Capsules, Multiple Ascending Dose (MAD)<br>* Other names: 7HP349 MAD;Drug: 7HP349 Food Effect<br>* Part C: 7HP349 Capsules, Food Effect<br>* Other names: 7HP349 FE;|
| Placebo Comparator: Placebo Capsules<br>Part A: Placebo Capsules (5 cohorts); Part B: Placebo Capsules (2 cohorts) | Drug: Placebo Single Ascending Dose<br>* Part A: Placebo Capsules, Single Ascending Dose (SAD)<br>* Other names: Placebo SAD;Drug: Placebo Multiple Ascending Dose<br>* Part B: Placebo Capsules, Multiple Ascending Dose (MAD)<br>* Other names: Placebo MAD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of 7HP349 in healthy male subjects as assessed by incidence of treatment-emergent adverse events according to CTCAE v5.0 criteria | Safety assessments will include evaluation of incidence of treatment-emergent adverse events (AEs) according to CTCAE v5.0 criteria, including vital signs, resting electrocardiogram (ECG) parameters, standard hematology, chemistry, urinalysis and other tests | 17 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of 7HP349 in healthy male subjects as assessed by maximum plasma concentration (Cmax) towards determination of the optimal pharmacokinetic dose (OPD) | Determination of maximum plasma concentration (Cmax) | 17 days | 
| Pharmacokinetics of 7HP349 in healthy male subjects as assessed by plasma exposure (AUClast and/or AUCinf) towards determination of the optimal pharmacokinetic dose (OPD) | Determination of plasma exposure (AUClast and/or AUCinf) | 17 days | 
| Pharmacokinetics of 7HP349 in healthy male subjects as assessed by exposure in urine towards determination of the optimal pharmacokinetic dose (OPD) | Determination of exposure in urine | 17 days | 
| Pharmacokinetics of 7HP349 in healthy male subjects as assessed by renal clearance (CLr) towards determination of the optimal pharmacokinetic dose (OPD) | Determination of renal clearance (CLr) | 17 days | 
| Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma concentration (Cmax) in fed individuals | Fed prandial state, determination of maximum plasma concentration (Cmax) | 28 days | 
| Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma exposure (AUClast and/or AUCinf) in fed individuals | Fed prandial state, determination of plasma exposure (AUClast and/or AUCinf) | 28 days | 
| Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma concentration (Cmax) in fasted individuals | Fasted prandial state, determination of maximum plasma concentration (Cmax) | 28 days | 
| Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma exposure (AUClast and/or AUCinf) in fasted individuals | Fasted prandial state, determination of plasma exposure (AUClast and/or AUCinf) | 28 days | 
| Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of the Geometric Mean Ratio (GMR) of the maximum plasma concentration (Cmax) in fed vs. fasted individuals | Determination of Geometric Mean Ratio (GMR) of fed:fasted Cmax | 28 days | 
| Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of the Geometric Mean Ratio (GMR) of the plasma exposure (AUClast and/or AUCinf) in fed vs. fasted individuals | Determination of Geometric Mean Ratio (GMR) of fed:fasted AUClast and/or AUCinf | 28 days |