NCT02115347已完成1 期
A Phase 1, Non-randomized, Open-label, Single Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Subjects With Hepatic Impairment and the Healthy Subjects With Normal Hepatic Function
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
研究概览
简要总结
This is a study to assess the pharmacokinetics and safety of ertugliflozin (MK-8835, PF-04971729) in participants with hepatic impairment versus healthy participants. In Part 1 of the study, participants with moderate hepatic impairment (Child-Pugh score 7-9) and matched healthy participants will be enrolled; depending on results in Part 1, Part 2 may be conducted and will enroll participants with mild hepatic impairment (Child-Pugh score 5-6).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •ALL PARTICIPANTS:
- •Body Mass Index (BMI) of 18 to 40 kg/m^2; and a total body weight >50 kg (110 lbs)
- •Male or female not of reproductive potential
- •If a female of reproductive potential, agrees to remain abstinent from heterosexual activity or agree to use or have their partner use 2 methods of acceptable contraception to prevent pregnancy while the participant is receiving study medication and for 14 days after the last dose of study medication PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
- •Healthy with normal hepatic function PARTICIPANTS WITH HEPATIC IMPAIRMENT
- •Satisfy the criteria for Child-Pugh classification [moderate (Part 1): Child-Pugh Scores 7-9 points, mild (Part 2): Child-Pugh Scores 5-6 points] within 14 days before administration of study medication
- •A diagnosis of hepatic impairment due to primary liver disease and not secondary to other diseases
- •Stable hepatic impairment, defined as no clinically-significant change in disease status within the last 30 days
- •On a stable dose of medication and/or treatment regimen used to manage hepatic disease for at least 4 weeks prior to study start
排除标准
- •ALL PARTICIPANTS
- •A known hypersensitivity or intolerance to ertugliflozin or any other Sodium-Glucose co-Transporter 2 (SGLT2) inhibitor (i.e., canagliflozin [Invokana], dapagliflozin [Farxiga], empagliflozin, or ipragliflozin)
- •Febrile illness within 5 days prior to the first dose of study medication
- •Any clinically significant malabsorption condition
- •A positive urine drug screen for drugs of abuse or recreational drugs
- •Abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of study start
- •Treatment with an investigational drug within 30 days preceding the first dose of study medication
- •Pregnant or breastfeeding females
- •Use of herbal supplements within 28 days prior to the first dose of study medication
- •Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing
- •History of sensitivity to heparin or heparin-induced thrombocytopenia PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
- •Use of prescription drugs (hormonal methods of birth control are allowed), vitamins, and dietary supplements within 7 days prior to the first dose of study medication
- •Positive serology for Hepatitis B or C PARTICIPANTS WITH HEPATIC IMPAIRMENT
- •Hepatic carcinoma and hepatorenal syndrome or life expectancy less than 1 year
- •Undergone portal-caval shunt surgery
- •History of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to study entry
- •Signs of significant hepatic encephalopathy
- •Severe ascites and/or pleural effusion
- •A transplanted kidney, heart or liver
- •Received any of the following medications within 7 days prior to the first dose of study medication or during the study: other SGLT2 inhibitors (eg, dapagliflozin, canagliflozin, empagliflozin, and ipragliflozin); any potent drug-metabolizing enzyme-inducing drug, including rifampin, phenytoin, and carbamazepine; probenecid, valproic acid, gemfibrozil
研究组 & 干预措施
Ertugliflozin 15 mg - Moderate Hepatic Impairment
Experimental
Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
干预措施: Ertugliflozin 15 mg (Drug)
Ertugliflozin 15 mg - Healthy Participants
Other
Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
干预措施: Ertugliflozin 15 mg (Drug)
Ertugliflozin 15 mg - Mild Hepatic Impairment
Experimental
Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
干预措施: Ertugliflozin 15 mg (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
时间窗: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (AUClast).
AUC From Hour 0 to Infinity (AUCinf) for Ertugliflozin
时间窗: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf).
次要结局
- AUClast for Fraction of Ertugliflozin Unbound in Plasma (AUClast,u)(Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours)
- Maximum Plasma Concentration (Cmax) of Ertugliflozin(Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours)
- Cmax for Fraction of Ertugliflozin Unbound in Plasma (Cmax,u)(Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours)
- AUCinf for Fraction of Ertugliflozin Unbound in Plasma (AUCinf,u)(Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours)
- Number of Participants Who Experienced an Adverse Event(Up to 19 days)
研究者
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