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

Phase 1

Completed

Conditions: Smoking Cessation

Interventions: Drug: SBP-9330
Drug: Placebo

Registration Number: NCT04948827

Lead Sponsor: Camino Pharma, LLC

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 90

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A2 - Single-Dose (Active; 300 mg)	SBP-9330	In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort.
Part A5 - Single-Dose (Active; 600 mg)	SBP-9330	In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort.
Part A - Single-Dose (Placebo; pooled)	Placebo	In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort.
Part B2 - Multiple-Dose Active (225 mg)	SBP-9330	In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Part B - Multiple-Dose Placebo (pooled)	Placebo	In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Part C1 - Smoker Phase (Active; 150 mg)	SBP-9330	In Part C, cohorts of healthy smokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Part C2 - Smoker Phase (Active; 225 mg)	SBP-9330	In Part C, cohorts of healthy smokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Part C - Smoker Phase (Placebo; pooled)	Placebo	In Part C, cohorts of healthy smokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Part A1 - Single-Dose (Active; 150 mg )	SBP-9330	In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort.
Part A3 - Single-Dose Food Effect (Active; 225 mg)	SBP-9330	In this two-period food-effect cohort, each healthy nonsmoker subject received the randomly assigned treatment (SBP-9330 or placebo) under fasting conditions (Period 1). After a 7- to 14-day washout period, subjects received 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 were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort.
Part A4 - Single-Dose (Active; 450 mg)	SBP-9330	In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort.
Part B1 - Multiple-Dose Active (150 mg)	SBP-9330	In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Part B3 - Multiple-Dose Active (300 mg)	SBP-9330	In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.

Primary Outcome Measures

Name	Time	Method
Number of Treatment-Emergent Adverse Events [Safety and Tolerability]	Part A: 8 days Part B: 21 days Part C: 21 days	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

Secondary Outcome Measures

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