A First-in-Human Study of SBP-9330 in Healthy Subjects

Study Overview
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Brief Summary
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This is a single center, first-in-human, randomized, double-blind, placebo-controlled, Single-Ascending Dose (SAD) / Multiple-Ascending Dose (MAD) study incorporating a food-effect cohort.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of SBP-9330 (With a Nested Food-Effect Arm) After Oral Administration in Healthy Subjects

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: SBP-9330
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent prior to the initiation of any protocol-specific procedures Stated willingness to comply with all study procedures and availability for the duration of the study Healthy male or female subject ≥ 18 and ≤ 55 years of age Body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 32.0 kg/m2 Body weight ≥ 50.0 kg at Screening A female subject must meet at least one of the following criteria: a. Is of childbearing potential and agrees to use an acceptable contraceptive method. b. Is of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (i.e., at least 1 year without menses prior to the first study drug administration without an alternative medical condition and confirmed with a serum follicle-stimulating hormone [FSH] > 40 IU/L at Screening) Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from the first admission to the CRU until 90 days after the last study drug administration. Part A and B only: Never- or nonsmoker (a nonsmoker is defined as someone who completely stopped using nicotine products for at least 2 years prior to the first study drug administration) Have no clinically significant medical or mental health conditions captured in the medical history or evidence of clinically significant findings on the physical examination and/or ECG, as determined by an Investigator No clinically significant abnormalities in blood pressure, heart rate, body temperature and respiratory rate and no evidence of orthostatic hypotension or postural tachycardia at Screening. Part C Only: Are current tobacco cigarette smokers who smoke an average of 10 or more cigarettes per day in the 30 days prior to Screening Expired breath CO level ≥10 parts per million (ppm) at Screening and prior to the first study drug administration Positive test result for cotinine at Screening and prior to the first study drug administration Are not motivated to try to quit smoking from Screening through 30 days from the first study drug administration Exclusion Criteria: Female who is lactating Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration Female who is planning to become pregnant during this study or within 90 days after the last study drug administration Male with female partner who is pregnant, lactating, or planning to become pregnant during this study or within 90 days after the last study drug administration Poor venous access as determined by an Investigator at Screening History of significant hypersensitivity to SBP-9330 or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs Presence of any medical condition that, in the opinion of an Investigator, poses an unacceptable risk to the subjects Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug absorption Evidence or history of clinically significant cardiovascular, pulmonary, hematologic, psychiatric (including mood and substance use disorders), neurological (including migraines, seizures, and epilepsy), endocrine, renal, hepatic, gastrointestinal, immunologic or dermatologic disease History of malignancy within the past five years, except for successfully treated basal cell carcinoma of the skin History of suicidal ideation or suicidal behavior as per the C-SSRS questionnaire administered at Screening Evidence or history of significant psychiatric disease or any DSM-5 disorder as assessed by the Mini International Neuropsychiatric Interview (M.I.N.I.) administered at Screening Routine or chronic use of more than three grams of acetaminophen daily Strenuous activity, sunbathing, and contact sports within 48 hours prior to (first) admission to the CRU Current alcohol consumption exceeding two standard drinks per day on average (1 standard drink=10 grams of alcohol) for male subjects and one standard drink per day on average for female subjects History of alcohol or drug (other than caffeine) use disorder within 12 months prior to Screening Any clinically significant illness in the 28 days prior to the first study drug administration QTcF interval (QT interval corrected for heart rate according to Fridericia) > 450 ms for males and > 470 ms for females at Screening or on Day -1 Parts A and B only: Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration Positive test results for HIV-1/HIV-2 antibodies, hepatitis B surface antigen or hepatitis C antibody Consumption of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) or over-the-counter medications and nutrients known to modulate cytochrome P450 (CYP450) enzymes activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange products) or St. John's Wort within 14 days prior to the first study drug administration Consumption of other prescription and over-the-counter medication not specifically excluded by Exclusion Criterion 21 including health supplements and herbal remedies within 7 days prior to the first study drug administration (an exception is made for paracetamol [acetaminophen], which is allowed up to admission to the clinic). Any other clinically significant abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data Intake of an investigational product in the 30 days or 5 half-lives (whichever is longer) prior to Screening Inclusion in a previous cohort of this clinical study Employee of the contract research organization (CRO) or the Sponsor. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to Screening Plasma donation within 7 days prior to Screening Part C Only: History of generalized rash reaction to any drugs Positive test result (except cotinine) for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration Use of smoking cessation aids (NRT, bupropion, or varenicline) within 30 days prior to the first study drug administration Unable to abstain from smoking tobacco cigarettes for at least 1 hour before and 2 hours after study drug administration Unable to abstain from using nicotine-containing products other than tobacco cigarettes (e.g., pipes, cigars, e-cigarettes or vapes, nicotine topical patches, nicotine gum, or nicotine lozenges) during the study

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Single-Dose (Active)<br>In Part A, cohorts of healthy nonsmokers will be randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects will be randomized and dosed ahead of the rest of the cohort. A review of safety data will be completed prior to administration of doses to the remainder of the cohort. | Drug: SBP-9330<br>* SBP-9330 oral capsules<br>|
| Placebo Comparator: Part A - Single-Dose (Placebo)<br>In Part A, cohorts of healthy nonsmokers will be randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects will be randomized and dosed ahead of the rest of the cohort. A review of safety data will be completed prior to administration of doses to the remainder of the cohort. | Drug: Placebo<br>* Placebo oral capsules<br>|
| Experimental: Part A - Single-Dose Food-Effect (Active)<br>In this two-period food-effect cohort, each healthy nonsmoker subject will receive the randomly assigned treatment (SBP-9330 or placebo) under fasting conditions (Period 1). After a 7- to 14-day washout period, subjects will receive the same single dose of SBP-9330 or placebo in a fed state (Period 2) 30 minutes after the start of an FDA High-Fat and High-Calorie Breakfast. A sentinel group of 2 subjects will be randomized and dosed ahead of the rest of the cohort. A review of safety data will be completed prior to administration of doses to the remainder of the cohort. | Drug: SBP-9330<br>* SBP-9330 oral capsules<br>|
| Placebo Comparator: Part A - Single-Dose Food-Effect (Placebo)<br>In this two-period food-effect cohort, each healthy nonsmoker subject will receive the randomly assigned treatment (SBP-9330 or placebo) under fasting conditions (Period 1). After a 7- to 14-day washout period, subjects will receive the same single dose of SBP-9330 or placebo in a fed state (Period 2) 30 minutes after the start of an FDA High-Fat and High-Calorie Breakfast. A sentinel group of 2 subjects will be randomized and dosed ahead of the rest of the cohort. A review of safety data will be completed prior to administration of doses to the remainder of the cohort. | Drug: Placebo<br>* Placebo oral capsules<br>|
| Experimental: Part B - Multiple-Dose (Active)<br>In Part B, cohorts of healthy nonsmokers will be randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. | Drug: SBP-9330<br>* SBP-9330 oral capsules<br>|
| Placebo Comparator: Part B - Multiple-Dose (Placebo)<br>In Part B, cohorts of healthy nonsmokers will be randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. | Drug: Placebo<br>* Placebo oral capsules<br>|
| Experimental: Part C - Smoker Phase (Active)<br>In Part C, cohorts of healthy smokers will be randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. | Drug: SBP-9330<br>* SBP-9330 oral capsules<br>|
| Placebo Comparator: Part C - Smoker Phase (Placebo)<br>In Part C, cohorts of healthy smokers will be randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. | Drug: Placebo<br>* Placebo oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Number of drug-related adverse events as determined by clinically significant changes in vital signs, physical examination findings, ECG parameters, C-SSRS questionnaire results, and clinical laboratory results | Up to 52 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of SBP-9330: Cmax | Maximum observed concentration (Cmax) | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: Tmax | Time to reach maximum observed concentration (Tmax) | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: AUC 0-24 | Area under the concentration time curve from time 0 (dose administration) to 24 hours | PK samples will be obtained at selected timepoints from pre-dose until 24 hours post-dose | 
| Pharmacokinetics of SBP-9330: AUC 0-T | Area under the concentration time curve from time 0 (dose administration) to the time of last quantifiable concentration | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: AUC 0-∞ | Area under the concentration time curve extrapolated to infinity | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: T½ | Terminal elimination half-life | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: CL/F | Apparent total clearance | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: Vz/F | Apparent volume of distribution | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: C trough | Observed concentration at the end of the dosing interval | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: Cτ | Concentration at the end of the dosing interval. | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: AUCτ | Area under the concentration time curve over the dosing interval at steady state, calculated from 0 to 24 hours (dosing interval) | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: T½, eff | Effective half-life | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: CL/Fss | Apparent total clearance at steady state | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: Vz/Fss | Apparent volume of distribution at steady state | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: RAC(Cmax) | Accumulation ratio evaluated by comparing Day 14 Cmax to Day 1 Cmax | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose | 
| Pharmacokinetics of SBP-9330: RAC(AUC) | Accumulation ratio evaluated by comparing Day 14 AUCτ to Day 1 AUC0-24 | PK samples will be obtained at selected timepoints from pre-dose until 48 hours post-dose |