A Phase 1, Placebo-Controlled, Double-Blind, Dose-Escalation Study To Investigate The Safety, Tolerability, And Pharmacokinetics Of A Single Intravenous Dose Of GMA301 Injection In Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- GMA301 Injection
- Conditions
- Pulmonary Arterial Hypertension
- Sponsor
- Gmax Biopharm Australia Pty Ltd.
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Safety and Tolerability
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This study is a single-centre, randomized, double-blind, placebo-controlled, dose escalation study to assess the safety, tolerability and PK of GMA301 Injection in healthy subjects. Two sequential dosing cohorts (at ascending dose fashion), each with 6 subjects receiving GMA301 Injection and 2 subjects receiving placebo (total of 16 subjects), will be given single doses. The doses to be administered in the two cohorts will be 1500 mg and 2000 mg respectively, or matching placebo
Detailed Description
The current study is an extension of the previous study #1010218 (ACTRN12618000121268) to further explore the safety and PK profile of GMA301 injection at higher dosage. The SRC (Safety Review Committee) will be responsible for the assessment of safety, tolerability, and PK data for each dose level and to make decisions with regards to study progression. A Statistical Analysis Plan (SAP) will be written after finalizing the protocol and prior to database lock. The SAP will detail the implementation of all the planned statistical analyses in accordance with the principal features stated in the protocol. Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Non-smoker (no use of tobacco or nicotine products within 2 months prior to screening) with BMI \> 18.5 and \< 30.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females. Each cohort will include at least 2 participants of Chinese descent, if possible.
- •Healthy as defined by:
- •The absence of clinically significant illness and surgery within 4 weeks prior to dosing.
- •The absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
- •Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for 6 months after the last study drug administration:
- •Oral, injected, or implanted hormonal methods of contraception in combination with a barrier method;
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS) in combination with a barrier method;
- •Sterilized male partner (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) in combination with a barrier method;
- •True abstinence, when this is in line with the subject's preferred and usual lifestyle.
- •Male subjects must agree to avoid causing pregnancy by using a reliable method of birth control during the study and for 6 months after study drug administration and must be willing to use one of the following acceptable contraceptives:
Exclusion Criteria
- •Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C found during medical screening.
- •Presence or history of any clinically significant chronic condition of the neurological, respiratory, cardiovascular, gastrointestinal, urogenital, reproductive, musculoskeletal, endocrine system or cancer.
- •Clinically significant (as judged by the investigator) presence of acute illness (e.g., gastrointestinal illness, infection such as influenza, upper respiratory tract infection) upo admission to the study site.
- •Alanine aminotransferase and/or aspartate aminotransferase above the upper limit of normal.
- •Positive urine drug screen or alcohol breath test at screening.
- •Positive pregnancy test at screening.
- •Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 60 or over 90 mmHg,or heart rate less than 40 or over 100 bpm) at screening. Up to 2 additional measurements may be taken after an appropriate resting interval (at least 10 minutes) at Screening to confirm eligibility.
- •History of type 1 hypersensitivity or severe cutaneous adverse reaction to any medication, or to any excipient in the formulation, or history of significant atopy.
- •Hemoglobin below lower limit of normal.
- •Women who intend to become pregnant or are lactating.
Arms & Interventions
GMA301 1500mg Or Placebo Injection
Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 1500 mg single Intravenous dose of GMA301 Injection.
Intervention: GMA301 Injection
GMA301 1500mg Or Placebo Injection
Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 1500 mg single Intravenous dose of GMA301 Injection.
Intervention: GMA301 Placebo Injection
GMA301 2000mg Or Placebo Injection
Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 2000 mg single intravenous dose of GMA301 Injection.
Intervention: GMA301 Placebo Injection
GMA301 2000mg Or Placebo Injection
Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 2000 mg single intravenous dose of GMA301 Injection.
Intervention: GMA301 Injection
Outcomes
Primary Outcomes
Safety and Tolerability
Time Frame: All AEs (adverse events) will be captured from the time the investigator received the signed ICF (informed consent form) of subjects until study completion ie Day 70
To assess the safety and tolerability of GMA301 Injection following single escalating intravenous (IV) injections in healthy subjects.
Secondary Outcomes
- Dose for GMA301 Injection for subsequent clinical studies(All AEs will be captured from the time the investigator received the signed ICF of subjects until study completion ie Day 70)
- Pharmacokinetics Profile(Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70)