The Effect of Tasisulam on the CYP2C9-Mediated Metabolism of Tolbutamide: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)
研究概览
简要总结
The purpose of this study was to assess the effect of tasisulam as an inhibitor of CYP2C9, using tolbutamide as a probe substrate. This study was to have 3 treatment periods, and continued access in an extension period. Period 1 is 4 days in length. Periods 2 and 3 are each approximately 28 days in length. Due to the early termination of the trial, only 1 Period 3 participant enrolled in the extension period before study termination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have histologically or cytologically confirmed solid malignancy or lymphoma that is advanced and/or metastatic disease which has not responded to standard therapy or for which no standard therapy exists.
- •Have given written informed consent prior to any study-specific procedures.
- •Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and an estimated life expectancy of greater than 12 weeks.
- •Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (45 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Limited field radiotherapy is permitted (in consultation with the investigator).
- •Have adequate organ function.
- •Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
- •Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug.
- •Females with child-bearing potential must have had a negative serum pregnancy test less than 7 days prior to the first dose of study drug.
排除标准
- •Have received treatment within 30 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.
- •Have known allergies to tasisulam or related compounds.
- •Have serious preexisting medical conditions.
- •Show evidence of significant active neuropsychiatric disease or central nervous system (CNS) disease (for example, Alzheimer's disease or Parkinson's disease). Patients with active brain metastasis are excluded.
- •Have current acute or chronic leukemia.
- •Females who are pregnant or lactating.
- •Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb).
- •History of severe allergies or multiple adverse drug reactions.
- •Are persons who have previously completed or withdrawn from this study or any other study investigating tasisulam.
- •Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study.
- •Serious concomitant systemic disorder, including diabetes or active infection, incompatible with the study.
- •Clinically significant cardiac symptomology.
- •Patients being treated with warfarin.
- •Patients being treated with sulfonylureas
- •Regularly use drugs of abuse and/or show positive findings on urinary drug screening that is not in accordance with known/acceptable concomitant medication.
- •Patients who have received medications that are known inducers or inhibitors of CYP2C9 within 30 days prior to enrollment.
- •Have donated or lost blood of more than 500 milliliter (mL) within the last month.
- •Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females) (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
- •Failure for any reason to satisfy the investigator for adequate fitness to participate in the study.
- •Screening albumin levels less than 30 grams/Liter (g/L).
研究组 & 干预措施
Tasisulam and Tolbutamide
Three study periods and continued access to tasisulam every 28 days (except Period 1 which was tolbutamide only and lasted 4 days) until disease progression:
Period 1: 500 milligram (mg) tolbutamide administered on Day 1.
Period 2: 500 mg of tolbutamide and individualized tasisulam dose [based on area under the curve albumin-corrected threshold (AUCalb)]. The AUCalb is a surrogate marker for unbound tasisulam, and this dosing approach represents the maximum level of unbound tasisulam which may be achieved clinically, administered on Day 1.
Period 3: Individualized tasisulam dose (based on AUCalb) administered on Day 1 and 500 mg tolbutamide administered on Day 4.
干预措施: Tolbutamide (Drug)
Tasisulam and Tolbutamide
Three study periods and continued access to tasisulam every 28 days (except Period 1 which was tolbutamide only and lasted 4 days) until disease progression:
Period 1: 500 milligram (mg) tolbutamide administered on Day 1.
Period 2: 500 mg of tolbutamide and individualized tasisulam dose [based on area under the curve albumin-corrected threshold (AUCalb)]. The AUCalb is a surrogate marker for unbound tasisulam, and this dosing approach represents the maximum level of unbound tasisulam which may be achieved clinically, administered on Day 1.
Period 3: Individualized tasisulam dose (based on AUCalb) administered on Day 1 and 500 mg tolbutamide administered on Day 4.
干预措施: Tasisulam (Drug)
结局指标
主要结局
Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)
时间窗: Period 2 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 120, 168, 336 hours post tolbutamide dose
AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
次要结局
- Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax)(Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose)
- Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞)(Period 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 24, 48, 96, and 264 hours post tolbutamide dose)
- Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)(Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose)