Clinical trial NCT04508179: A Phase 1 SAD and MAD Study of the Safety, Tolerability and PK of 7HP349 in Normal Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: 7 Hills Pharma, LLC
Sponsor class: INDUSTRY
Collaborators: name: Frontage Clinical Services, Inc.
First posted: 2020-08-11
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of 7HP349 in healthy male subjects as assessed by incidence of treatment-emergent adverse events according to CTCAE v5.0 criteria
timeFrame: 17 days
Secondary outcomes:
measure: Pharmacokinetics of 7HP349 in healthy male subjects as assessed by maximum plasma concentration (Cmax) towards determination of the optimal pharmacokinetic dose (OPD)
timeFrame: 17 days
measure: Pharmacokinetics of 7HP349 in healthy male subjects as assessed by plasma exposure (AUClast and/or AUCinf) towards determination of the optimal pharmacokinetic dose (OPD)
timeFrame: 17 days
measure: Pharmacokinetics of 7HP349 in healthy male subjects as assessed by exposure in urine towards determination of the optimal pharmacokinetic dose (OPD)
timeFrame: 17 days
measure: Pharmacokinetics of 7HP349 in healthy male subjects as assessed by renal clearance (CLr) towards determination of the optimal pharmacokinetic dose (OPD)
timeFrame: 17 days
measure: Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma concentration (Cmax) in fed individuals
timeFrame: 28 days
measure: 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
timeFrame: 28 days
measure: Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma concentration (Cmax) in fasted individuals
timeFrame: 28 days
measure: 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
timeFrame: 28 days
measure: 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
timeFrame: 28 days
measure: 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
timeFrame: 28 days
Other outcomes:
Locations:
city: Secaucus
country: United States
facility: Frontage Clinical Services Inc.
state: New Jersey
Study officials:
References: