A PHASE I, SINGLE-CENTER, OPEN-LABEL, CROSSOVER STUDY OF THE EFFECT OF AVANAFIL ON THE PHARMACOKINETICS OF OMEPRAZOLE, DESIPRAMINE AND ROSIGLITAZONE IN HEALTHY MALE SUBJECTS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- VIVUS LLC
- 入组人数
- 60
- 主要终点
- To measure a composite of pharmacokinetic parameters of Omeprazole, Rosiglitazone and Desipramine.
研究概览
简要总结
This study will compare the pharmacokinetics of omeprazole, rosiglitazone and desipramine when administered with a single oral dose of avanafil in healthy male subjects.
详细描述
There will be three cohorts in this Phase I, single-center, open-label, crossover study:
Cohort A (omeprazole): This is a open-label, non-randomized, one-sequence crossover study design, in which 20 healthy male subjects will be enrolled and administered a single oral dose of 40 mg omeprazole once daily for 8 days (Days 1-8) plus a single oral dose of 200 mg avanafil on Day 8. On Days 7 and 8, avanafil and/or omeprazole doses will be administered following an overnight fast of at least 10 hours.
All subjects will be confined at the Clinical Research Unit the day prior to the omeprazole administration on Day 7 and will remain confined for approximately 13 hours following the dosing on Day 8. Blood samples for determination of plasma omeprazole concentrations will be obtained from all subjects at 0 (10 minutes pre-dose), 20, 40 minutes and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 7 and 8. Pre-dose blood samples for determination of omeprazole will also be taken in the morning on Days 5-6.
Cohort B (rosiglitazone): This is a randomized, open-label, two-period crossover study design, in which 20 male subjects will be randomized to receive the following treatments:
- Treatment A: a single oral dose of 8 mg rosiglitazone following an overnight fast of at least 10 hours.
- Treatment B: a single oral dose of 8 mg rosiglitazone plus a single oral dose of 200 mg avanafil following an overnight fast of at least 10 hours.
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 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Voluntarily consent to participate in the study (informed consent form must be signed and dated prior to any study related assessments).
- •Adult male subjects of 18 to 45 years of age inclusive.
- •A body weight of at least 50 kg and a body mass index (BMI) between 18 and 30 kg/m2, inclusive [BMI will be calculated as weight in kg/(height in m)2].
- •Subjects must be identified as CYP2D6 extensive metabolizers (determined by genotyping) for Cohort C only
- •Subjects are able to communicate with the investigator, and to understand and comply with all requirements of study participation.
- •Medically healthy, with no clinically significant screening results (e.g., laboratory profiles, medical histories, ECGs, physical exam, etc.), in the opinion of the investigator in consultation with the Sponsor.
- •Male subjects should be willing to use a condom and spermicide during sexual activity for 90 days after last dosing of avanafil and be willing to not donate sperm for 90 days after dosing.
排除标准
- •A history or presence of significant cardiovascular (including thromboembolic disorders), neurological, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the investigator.
- •Any clinically significant laboratory abnormalities as judged by the investigator. Inclusion of a subject with out of normal range laboratory values must be approved by VIVUS prior to subject enrollment.
- •A predisposition to priapism, such as subjects with sickle cell disease or blood dyscrasias.
- •Known history of cardiovascular or cerebrovascular event, any history of angina.
- •History or ECG evidence of any high-risk arrhythmia or ECG judged by the investigator to be clinically significant.
- •Hypertrophic obstructive or other clinically significant cardiomyopathy, moderate or severe cardiac valvular disease.
- •Subjects whose pulse is lower than 50 bpm at screening or 50 bpm prior to dosing for period 1 only.
- •Acute illness, especially any infection, within 2 weeks of dosing.
- •Systolic blood pressure < 90 or > 140 mmHg; diastolic blood pressure < 60 or > 95 mmHg at screening or on Day -1 (2 rechecks are allowed) for period 1 only.
- •History of retinitis pigmentosa or nonarteritic anterior ischemic optic neuropathy.
- •Hemoglobin < 12.0 g/dL.
- •Subjects with liver function tests > 1.5 ULN
- •Positive urine drug test and/or positive urine alcohol test at screening or on Day -
- •Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening.
- •Any history or presence of alcoholism or drug or substance abuse within 18 months or as defined by the investigator.
- •Allergy to or previously significant adverse events with PDE5 inhibitors, omeprzole, rosiglitazone and desipramine or their constituents.
- •Use of any prescription or over-the-counter (OTC) medication, including herbal products, within the 30 days prior to Day
- •Up to 2 g per day of acetaminophen is allowed at the discretion of the Investigator.
- •Use of any drug in Appendix 1 (drugs known to have clinical significance in inhibiting or inducing liver enzymes involved in drug metabolism [CYP P450]) within 30 days prior to Day
- •Blood donation or significant blood loss within 56 days prior to Day
- •Plasma donation within 14 days prior to Day
- •Any use of tobacco or nicotine products within 6 months prior to Day
- •Any subject who received an investigational drug within 30 days or six half-lives, whichever is longer, prior to Day
- •Evidence of any clinically significant medical, psychiatric, social or other condition by history, physical examination or laboratory studies that, in the opinion of the investigator, would contraindicate the administration of study medications, affect compliance, interfere with study evaluations, limit study participation, or confound the interpretation of study results.
- •Involvement in the planning and conduct of the study (applies to both VIVUS or designee staff, or staff at the investigational site).
研究组 & 干预措施
Omeprazole
Omeprazole with single dose of avanafil (200 mg)
干预措施: Omeprazole (Drug)
Rosiglitazone
Rosiglitazone with single dose of avanafil (200 mg)
干预措施: Rosiglitazone (Drug)
Desipramine
Desipramine with single dose of avanafil (200 mg)
干预措施: Desipramine (Drug)
结局指标
主要结局
To measure a composite of pharmacokinetic parameters of Omeprazole, Rosiglitazone and Desipramine.
时间窗: 0, 20, 40 minutes and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours post dose
AUC0-t, AUC0-inf, Cmax, tmax, half-life
次要结局
- To assess vital signs before, during and after dosing(In the morning at Screening, Days 1-8 and upon early termination)