Multiple Ascending Dose Study of NH102 in Healthy Subjects

Jiangsu Nhwa Pharmaceutical

Status and phase: Completed; Phase 1

Conditions: Depression

Treatments: Drug: Placebo; Drug: NH102

Study type: Interventional

Funder types: Industry

Identifiers

NCT07324408

NH102-12

Details and patient eligibility

About

The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of NH102 when administered as multiple oral dose at escalating dose levels in healthy participants.

Full description

The drug being tested in this study is called NH102. NH102 is being tested to treat people who have depression. This study will look at the safety, tolerability and PK of NH102 in healthy participants.

The study may enroll up to 30-40 participants. Participants will be randomly assigned within each cohort to receive NH102 or placebo which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need). The study consists of four dose groups: 3 mg (fixed dose), 10 mg (fixed dose), 15 mg (starting at 6 mg, then escalated to 10 mg, and finally to 15 mg), and 20 mg (starting at 10 mg, then escalated to 15 mg, and finally to 20 mg). Each group enrolls 10 subjects, with 8 receiving NH102 and 2 receiving placebo. For the third and fourth dose groups (15 mg and 20 mg) that follow a titration dosing regimen, each includes 2 sentinel subjects (both male). The two sentinel subjects may be dosed simultaneously. Only after both sentinel subjects complete all 17 doses (with a single dose administered on Day 9) and are observed for at least 24 hours, along with preliminary confirmation of safety, may the remaining subjects in the same dose group proceed with dosing.

Enrollment: 40 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Subjects aged between 18 and 45 (both inclusive) years old when signing the informed consent.
2. Healthy volunteers has a body weight ≥50 kg (for male) or ≥ 45kg (for female) and body mass index ≥18.5 and ≤28 kg/m2 at screening.
3. Subjects voluntarily participate and sign the informed consent after understanding the purpose, content, procedures and possible risks of the trial.
4. The subjects will be able to communicate well with the investigators, be willing and able to comply with the lifestyle restrictions specified in the protocol, and cooperate to complete the study.

Exclusion criteria

1. The investigator determined that the subjects' present medical history and past medical history had any disease or dysfunction that would affect the clinical trial, including but not limited to diseases of the central nervous system, cardiovascular system, respiratory system, digestive system, urinary system, endocrine system, hematological system, etc.
2. There is any surgical condition or disease that may significantly affect the absorption, distribution, metabolism and excretion of drugs, or may harm to the subjects participating in the trial; such as history of gastrointestinal operations (gastrectomy, gastroenterostomy, enterectomy, etc.), urinary tract obstruction or dysuria, gastroenteritis, digestive tract ulcers, history of gastrointestinal bleeding, etc.
3. Subjects with past history of allergy to drugs or allergic disease.
4. Subjects with currently or past history of mental disorders and brain functional disorders.
5. According to the Columbia suicide severity scale (C-SSRS), subjects were at risk of suicide or were at risk of suicide based on the clinical judgment of the researchers, or with past history of self-injurious behavior.
6. Subjects have history of drug abuse or positive urine drug tests at screening within 1 year prior.
7. Subjects have history of alcohol abuse(i.e.,criteria are per week consumption more than 14 standard units(1 unit =360mL beer or 45mL 40% alcohol of Chinese liquor or 150mL wine)or positive alcohol breath tests at screening within 1 year prior.
8. Average amount of daily smoking>5 cigarettes at screening 3 months prior.
9. Those who have special requirements for food, cannot follow a uniform diet or have difficulty swallowing.
10. Female subjects who are pregnant and lactating ; and those who refuse to use effective non-drug contraceptive measures (such as abstinence, intrauterine device) or have planned to donate sperm or ovum throughout the study period and within 3 months after the end of the study.
11. Abnormal vital signs, lab and ECG indicators, as determined by the researcher, and clinically significant (e.g., male QTC > 450ms female > 470ms,corrected by Friericia ).
12. Subjects who resting heart rate <55 beats/min or >100 beats/min; systolic blood pressure <90mmHg or >140mmHg; diastolic blood pressure <60mmHg or >90mmHg.
13. Subjects who hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV-Ab), or HIV antibody (HIV-Ab), or syphilis serum reaction (TRUST) is non-negative.
14. Subjects who participated in any clinical trial within 3 months before medication.
15. Subjects have history of blood donations of 400 mL within 3 months before enrollment; 200 mL within 1 month before enrollment; or have history of using blood products.
16. Subjects who had a history of surgery within 3 months prior to enrollment, or did not recover from surgery, or had an expected surgical plan during the study period.
17. Subjects who had taken any drugs, including prescription and over-the-counter drugs within 2 weeks prior to enrollment.
18. Subjects who directly related to this clinical trial.
19. Subjects have poor compliance or other problems that the researchers believe that it is not suitable for participating.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 4 patient groups

NH102 3mg

Experimental group

Description:

NH102 3mg or NH102 placebo-matching, tablet, orally, bid (at approximately 8:00 AM and 8:00 PM). The morning doses on D1 and D7 (around 8:00 AM) are to be given under fasting conditions. A total of 13 consecutive doses are administered. For fasting doses: fast for at least 10 hours before dosing, fast for 4 hours after dosing, and no water intake 1 hour before and 1 hour after dosing.

Treatment:

Drug: NH102

Drug: Placebo

NH102 10mg

Experimental group

Description:

NH102 10mg or NH102 placebo-matching, tablet, orally, bid (at approximately 8:00 AM and 8:00 PM). The morning doses on D1 and D7 (around 8:00 AM) are to be given under fasting conditions. A total of 13 consecutive doses are administered. For fasting doses: fast for at least 10 hours before dosing, fast for 4 hours after dosing, and no water intake 1 hour before and 1 hour after dosing.

Treatment:

Drug: NH102

Drug: Placebo

NH102 15mg (6 mg→10 mg→15 mg）

Experimental group

Description:

NH102 6/10/15 mg or NH102 placebo-matching, tablet, orally, bid (at approximately 8:00 AM and 8:00 PM). Days 1-2: 6 mg, bid; Days 3-5: 10 mg, bid; Days 6-9: 15 mg, bid (administered only once on Day 9), for a total of 17 consecutive doses. The morning doses on D1 and D9 (around 8:00 AM) are to be given under fasting conditions. For fasting doses: fast for at least 10 hours before dosing, fast for 4 hours after dosing, and no water intake 1 hour before and 1 hour after dosing.

Treatment:

Drug: NH102

Drug: Placebo

NH102 20mg (10 mg→15 mg→20 mg）

Experimental group

Description:

NH102 10/15/20 mg or NH102 placebo-matching, tablet, orally, bid (at approximately 8:00 AM and 8:00 PM). Days 1-2: 10 mg, bid; Days 3-5: 15 mg, bid; Days 6-9: 20 mg, bid (administered only once on Day 9), for a total of 17 consecutive doses. The morning doses on D1 and D9 (around 8:00 AM) are to be given under fasting conditions. For fasting doses: fast for at least 10 hours before dosing, fast for 4 hours after dosing, and no water intake 1 hour before and 1 hour after dosing.

Treatment:

Drug: NH102

Drug: Placebo