The Phase I Study of HS-10509 in Chinese Adult Subjects

NCT06301074 | Not Yet Recruiting Phase 1

• 1 other identifier: HS-10509-101
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The study is to evaluate the safety, tolerability, and PK characteristics following single administration of HS-10509 in healthy adults, and multiple administrations of HS-10509 in patients with schizophrenia. Participants will have HS-10509 tablets or placebo once in the single ascending dose (SAD) part or once daily for 28 days in the multiple ascending dose (MAD) part.

Conditions

Schizophrenia

Keywords

Schizophrenia; Psychotropic drugs; Antipsychotic agents

Outcome Measures

Primary Outcomes (9)

• Incidence and severity of adverse events(AE) , serious AEs and AE leading to withdrawal from treatment.

  An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect.

  SAD: Baseline to Day 6; MAD: Baseline to Day 42

• Changes from baseline in lab tests

  Laboratory tests include blood routine, urine routine, blood biochemistry, coagulation function and serum prolactin, etc.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35

• Changes from baseline in vital signs

  Vital signs include blood pressure (BP), pulse rate, respiration and body temperature.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35

• Change from baseline in body weight

  Body weight was measured in kilograms (Kg).

  SAD: Baseline to Day 6; MAD: Baseline to Day 29

• Change from baseline in Electrocardiogram (ECG)

  ECG parameters including heart rate, PR interval, RR interval and QTcF, etc.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35;

• Change from Baseline in Columbia - Suicide Severity Rating Scale (C-SSRS)

  C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors, and has a binary response (yes/no). Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: Wish to be Dead, Non-specific Active Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act, Active Suicidal Ideation with Some Intent to Act, without Specific Plan, Active Suicidal Ideation with Specific Plan and Intent. Suicidal Behavior: a "yes" answer to any of 5 suicidal behavior questions: Preparatory Acts or Behavior, Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), Completed Suicide.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35

• Change from baseline in Abnormal Involuntary Movement Scale (AIMS)

  AIMS is a rating scale measuring involuntary movements known as tardive dyskinesia, that sometimes develop as a side effect of long-term treatment with antipsychotic medications. The AIMS score was calculated as the sum of questions 1 through 7 of the AIMS instrument, which includes assessments of involuntary movements in the face, lips, jaw, tongue, upper and lower extremities, and neck/shoulders/hips. Each item is rated on a five-point scale of severity from 0-4 with 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Total scores range from 0 to 28.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35

• Change from baseline in Barnes Akathisia Rating Scale (BARS)

  BARS is a rating scale that is administered by physicians to assess the severity of drug-induced akathisia, which is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting. The following subcategories are scored: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness and are rated on a 4-point scale from 0-3. In addition, the global clinical assessment of akathisia uses a 6-point scale ranging from 0-5. Total score ranges from 0 to 14 with a higher score indicating increased severity.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35

• Change from baseline in Simpson-Angus Scale (SAS)

  SAS is a 10-item testing instrument used to evaluate drug-related extrapyramidal syndromes. The following items are included in the SAS: gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella reflex, tremor, and salivation. Total score ranges from 0 to 40 with a higher score indicating increased severity.

  SAD: Baseline to Day 6; MAD: Baseline to Day 35

Secondary Outcomes (15)

• Cmax

  SAD: up to Day3

• Tmax

  SAD: up to Day3

• AUC0-t

  SAD: up to Day3; MAD: up to Day 30

• AUC0-∞

  SAD: up to Day3; MAD: up to Day 30

• λz

  SAD: up to Day3

Study Arms (4)

HS-10509 in healthy adults

EXPERIMENTAL

In SAD, participants in each dose-escalation cohort will orally receive a single dose of HS-10509 or a matching placebo on Day 1

Drug: HS-10509

Placebo in healthy adults

PLACEBO COMPARATOR

In SAD, participants in each dose-escalation cohort will orally receive a single dose of HS-10509 or a matching placebo on Day 1

Drug: Placebo

HS-10509 in patients

EXPERIMENTAL

In MAD, patient with schizophrenia in each dose-escalation cohort will orally receive HS-10509 or a matching placebo once daily for 28 days.

Drug: HS-10509

Placebo in patients

PLACEBO COMPARATOR

In MAD, patient with schizophrenia in each dose-escalation cohort will orally receive HS-10509 or a matching placebo once daily for 28 days.

Drug: Placebo

Interventions

HS-10509 DRUG

In SAD, participants will be assigned to receive either HS-10509 or a matching placebo for a single administration. There are 5 predefined dose cohorts (each cohort including 8 for HS-10509 and 2 for placebo), initially starting at 10 mg for cohort 1. In MAD, participants will assigned to receive HS-10509 or a matching placebo once daily for 28 days. There will be 3 dose cohorts (each cohort including 8 for HS-10509 and 2 for placebo), and the dose for each cohort is to be determined.

HS-10509 in healthy adults; HS-10509 in patients

Placebo DRUG

In SAD, participants will be assigned to receive either HS-10509 or a matching placebo for a single administration. There are 5 predefined dose cohorts (each cohort including 8 for HS-10509 and 2 for placebo), initially starting at 10 mg for cohort 1. In MAD, participants will assigned to receive HS-10509 or a matching placebo once daily for 28 days. There will be 3 dose cohorts (each cohort including 8 for HS-10509 and 2 for placebo), and the dose for each cohort is to be determined.

Placebo in healthy adults; Placebo in patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1(SAD) for healthy adults
• When signing the ICF, the subject should be between 18 and 45 years old (inclusive);
• Have a full understanding of the trial content, process and possible adverse reactions, be willing and able to abide by the contraindications or restrictions stipulated in this program, and voluntarily sign the ICF;
• Male weight ≥50kg, female weight ≥45kg, body mass index (BMI= weight/height 2\[kg/m2\]) in the range of 18-28 (inclusive);
• Agree to use (or have their partner use) an effective contraceptive method from the date of signing the ICF until 90 days after the last dose, and there are no plans to donate eggs/sperm.
• Part 2 (MAD) for Schizophrenia patients
• When signing the ICF, the subject is between 18 and 65 years old (inclusive);
• BMI at screening and baseline was between 18.5 and 30.0 kg/m2 (inclusive), and male subjects were ≥50 kg and female subjects were ≥45 kg;
• Meet the diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnostic criteria for schizophrenia;
• The total score of PANSS during screening and baseline was ≤90 points;
• Clinical overall impression - severity of disease (CGI-S) score ≤4 points;
• Currently not using antipsychotic drugs;
• Female subjects of reproductive age, screening and baseline urine pregnancy test results were negative;
• Female and male subjects of reproductive age and their spouses agree to use a highly effective contraceptive method during the study medication period and within 3 months after the termination of medication, and no sperm or egg donation is planned;
• After fully understanding the purpose, content, process and possible risks of this study, subjects and guardians shall voluntarily participate in this clinical study and sign a written informed consent, and are willing to complete the entire study process according to the requirements of the trial.

You may not qualify if:

• Part 1 (SAD) for healthy adults
• Other clinically significant diseases;
• After C-SSRS assessment, answer "yes" to question 4 or question 5 of the suicidal ideation questionnaire within 1 year, or have a history of suicidal behavior;
• allergies to multiple food or drug allergies, or known allergies to test drug ingredients;
• Within 2 weeks before the trial (or 5 half-lives of the drug, whichever is longer) or plan to take any medication during the trial, including prescription and over-the-counter drugs, Chinese herbal medicines, but not including vitamins, dietary supplements;
• Drug abusers or those who have used soft drugs (e.g., marijuana) within 3 months prior to the trial, or hard drugs (e.g., cocaine, PCP, etc.) within 1 year prior to the trial;
• Have a history of alcoholism or consume more than 14 units of alcohol per week in the last 2 weeks (1 unit = 285 mL for beer, 25 mL for spirits, 150 mL for wine);
• Smokers who smoked more than 5 cigarettes per day in the 3 months before the test, or could not stop using any tobacco products during the test;
• Blood donation or significant blood loss within 3 months before the first dose of the trial drug (≥450mL within 30 days, excluding blood collection at the screening stage), or a blood donation plan during the study period or within 3 months after the last visit;
• Those who had undergone surgery within 3 months prior to screening, or planned to undergo surgery during the study period; Or have undergone medical or surgical treatments that permanently alter the absorption, distribution, metabolism, and excretion of oral drugs (such as gastric or intestinal surgery);
• Participating in any clinical trial and taking any clinical trial drug within 3 months before the trial;
• Difficulty swallowing capsules and other solid preparations;
• The female subject is pregnant or breastfeeding, or the serum pregnancy test is positive;
• Difficulty in blood collection, unable to tolerate multiple intravenous blood collection and any blood contraindications;
• Positive baseline urine drug test, or positive alcohol breath test;

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, China

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Xiaojiao Li, Dr.

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lei Sun

CONTACT

+86 18652107831; sunl6@hspharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: For each cohort, participants will be assigned to receive HS-10509 or placebo in parallel

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 8, 2024
• Study Start: March 1, 2024
• Primary Completion: May 1, 2024
• Study Completion: October 1, 2024
• Last Updated: March 8, 2024

Record last verified: 2024-02

Locations

CN (1)