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

Camino Pharma

Status and phase: Completed; Phase 1

Conditions: Smoking Cessation

Treatments: Drug: Placebo; Drug: SBP-9330

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT04948827

U01DA051077 (U.S. NIH Grant/Contract)

SBP-9330-101

Details and patient eligibility

About

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.

Enrollment: 90 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Provision of written informed consent prior to the initiation of any protocol-specific procedures

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Healthy male or female subject ≥ 18 and ≤ 55 years of age

4. Body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 32.0 kg/m2

5. Body weight ≥ 50.0 kg at Screening

6. 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)

7. 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.

8. 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)

9. 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

10. 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:

11. Are current tobacco cigarette smokers who smoke an average of 10 or more cigarettes per day in the 30 days prior to Screening

12. Expired breath CO level ≥10 parts per million (ppm) at Screening and prior to the first study drug administration

13. Positive test result for cotinine at Screening and prior to the first study drug administration

14. Are not motivated to try to quit smoking from Screening through 30 days from the first study drug administration

Exclusion criteria

1. Female who is lactating

2. Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration

3. Female who is planning to become pregnant during this study or within 90 days after the last study drug administration

4. 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

5. Poor venous access as determined by an Investigator at Screening

6. 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

7. Presence of any medical condition that, in the opinion of an Investigator, poses an unacceptable risk to the subjects

8. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug absorption

9. 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

10. History of malignancy within the past five years, except for successfully treated basal cell carcinoma of the skin

11. History of suicidal ideation or suicidal behavior as per the C-SSRS questionnaire administered at Screening

12. 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

13. Routine or chronic use of more than three grams of acetaminophen daily

14. Strenuous activity, sunbathing, and contact sports within 48 hours prior to (first) admission to the CRU

15. 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

16. History of alcohol or drug (other than caffeine) use disorder within 12 months prior to Screening

17. Any clinically significant illness in the 28 days prior to the first study drug administration

18. 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

19. Parts A and B only: Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration

20. Positive test results for HIV-1/HIV-2 antibodies, hepatitis B surface antigen or hepatitis C antibody

21. 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

22. 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).

23. 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

24. Intake of an investigational product in the 30 days or 5 half-lives (whichever is longer) prior to Screening

25. Inclusion in a previous cohort of this clinical study

26. Employee of the contract research organization (CRO) or the Sponsor.

27. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to Screening

28. Plasma donation within 7 days prior to Screening

    Part C Only:

29. History of generalized rash reaction to any drugs

30. Positive test result (except cotinine) for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration

31. Use of smoking cessation aids (NRT, bupropion, or varenicline) within 30 days prior to the first study drug administration

32. Unable to abstain from smoking tobacco cigarettes for at least 1 hour before and 2 hours after study drug administration

33. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

90 participants in 13 patient groups, including a placebo group

Part A1 - Single-Dose (Active; 150 mg )

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part A3 - Single-Dose Food Effect (Active; 225 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part A2 - Single-Dose (Active; 300 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part A4 - Single-Dose (Active; 450 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part A5 - Single-Dose (Active; 600 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part A - Single-Dose (Placebo; pooled)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Part B1 - Multiple-Dose Active (150 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part B2 - Multiple-Dose Active (225 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part B3 - Multiple-Dose Active (300 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part B - Multiple-Dose Placebo (pooled)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Part C1 - Smoker Phase (Active; 150 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part C2 - Smoker Phase (Active; 225 mg)

Experimental group

Description:

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.

Treatment:

Drug: SBP-9330

Part C - Smoker Phase (Placebo; pooled)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo