A Phase I, Open-label, Randomized Crossover Study to Evaluate the Relative Bioavailability and the Effect of Food for Sotorasib Tablets in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Amgen
- 主要终点
- Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib
研究概览
简要总结
The primary objectives of the study are to compare the pharmacokinetics (PK) and demonstrate relative bioavailability of sotorasib administered as 4 oral tablets (test) to sotorasib administered as 8 oral tablets (reference) and to assess the effect of food on the PK of sotorasib administered as 4 oral tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female participants, between 18 and 60 years of age (inclusive), at the time of Screening.
- •Body mass index, between 18 and 32 kg/m2 (inclusive), at the time of Screening
- •Females of nonchildbearing potential
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) as assessed by the Investigator (or designee).
排除标准
- •Inability to swallow oral medication or history of malabsorption syndrome.
- •History of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) and in consultation with the Sponsor.
- •Poor peripheral venous access.
- •History or evidence, at Screening or Check in, of clinically significant disorder, condition, or disease, including not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
- •History or evidence of clinically significant arrhythmia at Screening, including any clinically significant findings on the ECG taken at Check-in.
- •History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration or bowel disease (including but not limited to peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease, or irritable bowel syndrome), or a history of gastrointestinal surgery other than uncomplicated appendectomy and hernia repair. History of cholecystectomy is not permitted.
- •Estimated glomerular filtration rate (eGFR) less than 70 mL/min/1.73 m² as calculated by the Modification of Diet in Renal Disease (MDRD) equation, at Screening or Check-in.
- •ALT or AST > ULN, at Screening or Check-in.
- •Thyroid-stimulating hormone outside normal range.
- •Positive hepatitis B or hepatitis C panel and/or positive human immunodeficiency virus test, at Screening. Participants whose results are compatible with prior immunity (vaccination or prior infection) may be included.
- •Use of any over-the-counter or prescription medications within 30 days or 5 half-lives (whichever is longer) before enrollment. Acetaminophen (paracetamol) (up to 2 g per day) for analgesia will be allowed. Hormone-replacement therapy (e.g., estrogen) will be allowed.
研究组 & 干预措施
Treatment Sequence BAC
Participants will be administered sotorasib orally in the following order:
Treatment B - as 8 tablets under fasting conditions (reference) Treatment A - as 4 tablets under fasting conditions (test) Treatment C - as 4 tablets under fed conditions (test)
干预措施: Sotorasib (Drug)
Treatment Sequence ABC
Participants will be administered sotorasib orally in the following order:
Treatment A - as 4 tablets under fasting conditions (test) Treatment B - as 8 tablets under fasting conditions (reference) Treatment C - as 4 tablets under fed conditions (test)
干预措施: Sotorasib (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib
时间窗: Approximately 9 days
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Sotorasib
时间窗: Approximately 9 days
Maximum Plasma Concentration (Cmax) of Sotorasib
时间窗: Approximately 9 days
次要结局
- Number of Participants who Experience a Serious Adverse Event (SAE)(Up to approximately 39 days)
- Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE)(Approximately 9 days)