Aom0319 MAD Study in Healthy Subjects
Study Details
Study Description
Brief Summary
This study consists of two parts, Parts A and B. Part A includes a multiple ascending dose(MAD) study in healthy Caucasian subjects. Part B includes a multiple ascending dose(MAD) study in healthy Chinese subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This trial was designed based on a single-dose escalation phase I clinical study of Aom0319 for antagonizing rocuronium bromide-induced neuromuscular blockade that has been completed in China. This study is a single-center, randomized, double-blind and placebo-controlled trial. Healthy Caucasian and Chinese subjects will receive multiple-dose administration through intravenous drip infusion of different doses of Aom0319 to evaluate its safety, tolerability and pharmacokinetics profile, to assess whether there are differences in PK profile between Caucasian and Chinese races.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A: Caucasian Cohort Three ascending dose levels(Cohort A1、Cohort A2 and Cohort A3) of either MAD Aom0319 (n=8) or placebo (n=2) |
Drug: Aom0319
Multiple Dose for intravenous drip infusion
Other Names:
|
| Experimental: Part B: Chinese Cohort One dose level of MAD Aom0319 (n=8) or placebo (n=2) based on the data of Cohort A2 collected in Part A. |
Drug: Aom0319
Multiple Dose for intravenous drip infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The number, severity and type of adverse events, including changes in vital signs, physical examinations, laboratory safety tests and ECGs [16 days max]
To evaluate the safety and tolerability of MAD of Aom0319 in healthy subjects
Secondary Outcome Measures
- Maximum plasma concentration in plasma (Cmax) [Day1-2]
Pharmacokinetics
- Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration in plasma (AUC0-t) [Day1-2]
Pharmacokinetics
- Area under the concentration-time curve extrapolated from time 0 to infinity in plasma (AUC0-∞) [Day1-2]
Pharmacokinetics
- Time of the maximum observed concentration in plasma (Tmax) [Day1-2]
Pharmacokinetics
- Terminal elimination half-life in plasma (t1/2) [Day1-2]
Pharmacokinetics
- Volume of distribution during the terminal phase in plasma (Vz) [Day1-2]
Pharmacokinetics
- Total clearance in plasma (CL) [Day1-2]
Pharmacokinetics
- Terminal elimination rate constant in plasma (λz) [Day1-2]
Pharmacokinetics
- Percentage of area under the concentration-time in plasma (AUC_%Extrap) [Day1-2]
Pharmacokinetics
- Mean residence time in plasma (MRT) [Day1-2]
Pharmacokinetics
- Cumulative amount of dose recovered in urine from time 0 to 24 hours (Ae0-24) [Day1-2]
Pharmacokinetics
- Cumulative percentage of dose recovered in urine from time 0 to 24 hours (fe0-24) [Day1-2]
Pharmacokinetics
- Renal clearance in urine (CLr) [Day1-2]
Pharmacokinetics
- Maximum plasma concentration at steady-state in plasma (Css,max) [Day9-10]
Pharmacokinetics
- Trough plasma concentration at steady-state in plasma (Css,min) [Day9-10]
Pharmacokinetics
- Mean plasma concentration over the dosing interval at steady-state in plasma (Css,av) [Day9-10]
Pharmacokinetics
- Area under the concentration-time curve over the dosing interval at steady-state in plasma (AUC0-tau) [Day9-10]
Pharmacokinetics
- Volume of distribution during the terminal phase in plasma (Vz) [Day9-10]
Pharmacokinetics
- Volume of distribution at steady-state in plasma (Vz,ss) [Day9-10]
Pharmacokinetics
- Total clearance at steady-state in plasma (CLss) [Day9-10]
Pharmacokinetics
- Accumulation ratio for AUC in plasma (AR AUC) [Day9-10]
Pharmacokinetics
- Accumulation ratio for Cmax in plasma (AR Cmax) [Day9-10]
Pharmacokinetics
- Peak-to-trough fluctuation at steady-state in plasma (Fluctuation%) [Day9-10]
Pharmacokinetics
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy male or female subjects ≥18 years and ≤55 years of age on the day of ICF signing.
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Part A only: subjects must be Caucasian, with biological parents and both sets of biological grandparents also Caucasian.
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Part B only: subjects must be Chinese, with biological parents and both sets of biological parents of Chinese descent. All biological parents and both sets of biological parents must be born in China
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Male subjects must have a body weight ≥50 kg and female subjects must have a body weight ≥45 kg. Body mass index (BMI; calculated as weight [kg]/height [m]2) must be ≥18.0 and≤ 32.0 kg/m2;
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In good health, as determined by medical history, physical examination, clinical laboratory evaluation, 12-lead ECG, and vital signs within normal range or deemed by the investigator to be not clinically significant;
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Willing to use effective methods of contraception (except for steroid contraceptives which are not permitted), and do not plan to become pregnant, impregnate a partner, or donate sperm or ova throughout the study and for 3 months following the end of the study. Female subjects must be non-pregnant (confirmed by a negative serum or urine pregnancy test), non-lactating, or be of non-childbearing potential (females who have been postmenopausal [defined as FSH ≥40 IU/L] for at least 12 consecutive months or who without a uterus are considered to have no potential for pregnancy);
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Willing and able to freely given informed consent by signing the ICF.
Exclusion Criteria
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History of hereditary bleeding disorders, coagulation disorders, non-traumatic bleeding requiring treatment, or thromboembolism; or currently have any disease that can cause bleeding (including coagulation disorder, thrombocytopenia [platelet count < 150×109/L] and prothrombin time-international normalized ratio >1.5);
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 1.5 × the upper limit of normal at screening or check-in;
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Abnormal ECG results which are judged as clinically significant by the investigator, or any of the following:
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QTcF interval (calculated as QTc=QT/[RR^0.33]) >430 ms for male subjects and > 450 ms for female subjects;
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Complete bundle branch block including left and/or right complete bundle branch block;
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Symptoms of acute or age variable myocardial infarction;
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ST-T changes suggestive of myocardial ischemia;
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First-degree (PR interval ≥200 m s), second-degree, or third-degree atrioventricular block;
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Abnormal blood pressure or heart rate (defined as systolic blood pressure >140 mmHg or <90 mmHg, diastolic blood pressure >90 mmHg or <50 mmHg, and heart rate <50 bpm or
100 bpm) during the study screening period and at check-in, which are judged as clinically significant by the investigator;
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Febrile illness or infection within 7 days prior to drug administration (Day 1);
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History of significant food or drug allergy or allergy history (including symptoms of allergic reaction, clinically significant skin diseases such as contact dermatitis or psoriasis, visible skin rashes, or asthma attacks during physical examination) which is judged as clinically significant by the investigator, or hypersensitivity to cyclodextrin;
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Subjects who have previously taken sugammadex sodium;
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Acute or chronic clinically significant infectious disease during the screening period or at check-in; or a positive hepatitis C antibody, human immunodeficiency virus antibody, hepatitis B surface antigen, or syphilis test at screening;
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History or manifestation of disease that, in the opinion of the investigator, renders the subject unsuitable for the study, including but notlimited to nervous system, cardiovascular, blood, lymphatic, immune, kidney, liver, gastrointestinal, respiratory, metabolic, and musculoskeletal disorders;
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History of tuberculosis (TB) or related infection that is active, latent, or inadequately treated, or positive TB test (QuantiFERON Gold);
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History of disseminated herpes zoster, disseminated herpes simplex, recurrent localized cutaneous herpes zoster (including one episode of cutaneous herpes zoster);
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Poor peripheral venous access, unable to tolerate venipuncture, or have a significant history of trypanaphobia or hemophobia;
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History of substance abuse including illicit drugs within 6 months prior to dosing (Day 1);
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Use of drugs of abuse (including but not limited to amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxy-methamphetamine [MDMA], morphine, ketamine, phencyclidine, and cannabinoids) within 3 months prior to dosing (Day 1) ;
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Those who have been dosed in a previous study or administration of an investigational drug within 1 month (or 5 half-lives, whichever is longer) prior to dosing (Day 1);
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Use of fusidic acid, toremifene citrate, tamoxifen citrate, clomiphene citrate, progesterone, norethisterone, testosterone, prednisone, including combination contraceptives that contain steroid hormones such as progesterone, other steroid hormones, or any drug which could affect the absorption or PK parameters of adamgammadex, from 7 days prior to dosing to discharge after the end dosing (Day 11);
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Donation or loss of blood exceeding 500 mL of blood within 56 days prior to dosing (Day 1), plan to donate blood or blood components during the study period, or have previously received blood products;
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In addition to these steroid drugs listed in 16, use of prescription drugs, over-the-counter drugs, Chinese herbal medicines, dietary supplements, or natural health products (including vitamins, minerals, and phytotherapeutic, herbal, and plant-derived preparations) from 2 weeks prior to dosing (Day 1) until check-in (Day -1).
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Administration of a vaccine within 4 weeks prior to dosing (Day 1) or plan to be vaccinated during the study;
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Smoke more than 5 cigarettes per day within 30 days prior to dosing (Day 1) or unable abstain from tobacco- or nicotine-containing products including nicotine during the study (Day -1 to the follow up call);
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Regular consumption of more than 21 units for men and 14 units forfemales of alcohol per week within 3 months prior to dosing (Day 1; where 1 unit of alcohol ≈ 360 mL of beer or 45 mL of spirits with an alcohol content of 40% or 150 mL of wine), or a positive result on the alcohol breath test at screening or Day -1 , or unable to abstain from alcohol during the study (from check-in to the follow up call );
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Daily regular consumption of tea, coffee, and/or caffeinated beverages exceeding 8 cups (where 1 cup = 250mL) within 3 months prior to dosing. Having chocolate-, caffeine-, or xanthine-containing products 48 hours prior to dosing;
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Consumption of substances known to induce or inhibit liver metabolic enzymes (including grapefruit, mango, dragon fruit, grapes or grape juice, oranges or orange juice that could affect drug absorption, distribution, metabolism, and excretion 48 hours prior to dosing;
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Participation in strenuous activity within 48 hours prior to dosing;
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Female subjects who are pregnant or breastfeeding, who have a positive serum or urine pregnancy test result; who are unable or unwilling to take contraceptive or abstinence measures approved by the investigator during the study; Females subjects who are women of Non-Child bearing potential (WONCBP) or their Vasectomised male partner or Same-sex partner who refuse to use a barrier form of contraception (e.g. condom, diaphragm) to protect against the transfer of the study drug in any bodily fluids;
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Considered unsuitable for inclusion in the study by the investigator.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amckaus PTY LTD.
Investigators
- Principal Investigator: Kristi Mclendon, PhD, Nucleus Network
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Amckaus