A Bioequivalence Study of Fixed-dose Combination Tablet of 5 Milligrams Saxagliptin/10 Milligrams Dapagliflozin Relative to Their Respective Individual Components Coadministered to Healthy Subjects in the Fasted State
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 36
- 主要终点
- Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
研究概览
简要总结
The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy subjects.
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
- 19 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed Informed Consent Form
- •Signed written informed consent must be obtained from the subjects in accordance with requirements of the study center's IRB or IEC before the initiation of any protocol-required procedures.
- •Target Population
- •Healthy subjects as determined by no clinically significant deviation from normal in medical history, psychiatric history, physical examination findings, vital sign measurements, 12-lead ECG measurements, physical measurements, and clinical laboratory test results.
- •Age and Reproductive Status
- •Males and females, ages 19 to 55 years, inclusive. To extent possible, the distribution of men and women between the sequences will be balanced
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
- •Women must not be breastfeeding. d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs saxagliptin and dapagliflozin plus 5 half lives of study drug dapagliflozin (the longer half life between the 2 drugs; 3 days) for a total of 3 days following treatment completion.
- •e) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs saxagliptin and dapagliflozin plus 5 half lives of dapagliflozin (the longer half life between the 2 drugs; 3 days) for a total of 3 days following treatment completion.
- •f) Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section
排除标准
- •Any significant acute or chronic medical illness.
- •Current or recent (within 3 months of study drug administration) gastrointestinal disease that could impact upon the absorption of study drug
- •Any other sound medical, psychiatric, and/or social reason as determined by the investigator
- •Any major surgery within 4 weeks of study drug administration.
- •Any prior GI surgery including cholecystectomy (remote history of appendectomy will not be exclusionary).
- •Current, recent (within 3 months of study drug administration), or remote history of pancreatitis.
- •Donation of blood or plasma to a blood bank or in a clinical study (except at screening visit) within 4 weeks before study drug administration.
- •Blood transfusion within 4 weeks of study drug administration. h) Inability to tolerate oral medication.
- •Inability to be venipunctured performed and/or tolerate venous access.
- •Use of tobacco- or nicotine-containing products (including, but not limited to, cigarettes, pipes, e-cigarettes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months before check-in.
- •Drug or alcohol abuse (within 2 years of study drug administration) as defined in the Diagnostic and Statistical Manual of Mental Disorders - 4th Edition, Diagnostic Criteria for Drug and Alcohol Abuse History of glucose intolerance or diabetes mellitus.
- •For females, history of chronic or recurrent urinary tract infection (UTI) (defined as 3 occurrences per year) or UTI in the past 3 months. For males, any UTI within the previous 5 years that has not been thoroughly evaluated and for which an explanation is not clear.
- •History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal mycotic infections.
- •Any other sound medical, psychiatric, and/or social reason as determined by the investigator.
- •Physical and Laboratory Test Findings
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECGs, or clinical laboratory determinations beyond what is consistent with the target population.
- •Abnormal urinalysis at screening (may repeat once). If the urinalysis is abnormal on Day -1 of Period 1, continuation in the study is up to the investigator's discretion. The CRO medical monitor should be consulted.
- •Glucosuria or hematoria at screening or Day -1 of Period 1, repeat is not permitted. d) A positive nicotine test (ie, cotinine).
- •e) Abnormal liver function tests (alanine or aspartate aminotransferase [ALT or AST, respectively], or total bilirubin).
- •f) Any of the following on 12-lead ECG prior to study drug administration, confirmed by repeat.
- •i) PR ≥ 210 ms ii) QRS ≥ 120 ms iii) QT ≥ 500 ms iv) QTcF ≥ 450 ms g) Positive urine screen for drugs of abuse. h) Positive urine alcohol test. i) Positive blood screen for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV)-1 or HIV-2 antibodies at screening.
- •Allergies and Adverse Drug Reaction
- •History of allergy or adverse reactions to DPP4 or SGLT inhibitors or related compounds.
- •History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
- •Other Exclusion Criteria
- •Prisoners or subjects who are involuntarily incarcerated.
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- •Inability to comply with restrictions and prohibited activities/treatments
研究组 & 干预措施
Treatment A
Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet
干预措施: Saxagliptin (Drug)
Treatment A
Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet
干预措施: Dapagliflozin (Drug)
Treatment B
Single oral dose of FDC (fixed-dose combination) tablet
干预措施: Saxagliptin (Drug)
Treatment B
Single oral dose of FDC (fixed-dose combination) tablet
干预措施: Dapagliflozin (Drug)
结局指标
主要结局
Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
时间窗: Day 1-3 (Period 1) and Day 8-10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Saxagliptin Maximum Observed Concentrations (Cmax)
时间窗: Day 1-3 (Period 1) and Day 8-10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Dapagliflozin Maximum Observed Concentrations (Cmax)
时间窗: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
时间窗: Day 1-3 (Period 1) and Day 8-10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
时间窗: Day 1-3 (Period 1) and Day 8-10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
时间窗: Day 1-3 (Period 1) and Day 8-10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
次要结局
未报告次要终点