E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess, in healthy subjects, the effect of a light or high-fat meal on the single dose pharmacokinetics of ATV 300 mg, when administered in combination with RTV 100 mg. |
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E.2.2 | Secondary objectives of the trial |
- To assess, in healthy subjects, the effect of a light or high-fat meal on the pharmacokinetics of a single dose of RTV 100 mg, when administered in combination with ATV 300 mg. - To assess, in healthy subjects, the safety of a single dose of ATV 300 mg when administered in combination with RTV 100 mg. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Signed written informed consent 2) Target population: a) Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations. b) Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. 3) Men and women, ages 18 to 50 years inclusive. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and after the study in such a manner that the risk of pregnancy is minimized. |
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E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for a period of at least 1 month before and after the study. b) WOCBP using a prohibited contraceptive method within 3 months of first study dose. c) Women who are pregnant or breastfeeding d) Women with a positive pregnancy test on enrollment or prior to study drug administration.
2) Medical History and Concurrent Diseases a) Any significant acute or chronic medical illness. b) Current or recent (within 3 months) gastrointestinal disease. c) Any major surgery within 4 weeks of first dose of study drug. d) Any gastrointestinal surgery that could impact upon the absorption of study drug. e) Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of first dose of study drug. f) Blood transfusion within 4 weeks of first dose of study drug. g) Inability to tolerate oral medication. h) Inability to be venipunctured and/or tolerate venous access. i) Recent (within 6 months) drug or alcohol abuse as defined in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse (see Protocol Appendix 4) j) Any other sound medical, psychiatric and/or social reason as determined by the Investigator. k) Smoking more than 10 cigarettes per day. l) History of nephrolithiasis. m) History of acute or chronic pancreatitis. n) History of any hemolytic disorders. o) Proven or suspected acute hepatitis. p) Known or suspected HIV, HBV or HCV infection.
3) Physical and Laboratory Test Findings a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations. b) Positive urine screen for drugs of abuse either at screening or before each dose of study drug. c) Positive blood screen for hepatitis B and/or C antibodies. d) Positive blood screen for HIV-1;-2 antibodies. e) Positive pregnancy test for females. f) Creatinine clearance (as estimated by method of Cockcroft and Gault) less than 80 mL/min. g) Liver enzymes (total bilirubin, alkaline phosphatase, AST, ALT) above the upper limit of normal. h) QTc interval > 450 msec for males or > 470 msec for females. i) Second- or third-degree A-V block or clinically relevant ECG abnormalities.
4) Allergies and Adverse Drug Reactions a) History of allergy to atazanavir, ritonavir or related compounds. b) History of any significant drug allergy. c) Inability to tolerate or history of allergy to any of the foods described in the standard light and high-fat meals.
5) Prohibited Therapies and/or Medications a) Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug. b) Use of any prescription drugs or over-the-counter acid controllers within 4 weeks of first dose of study drug. c) Use of any other drugs, including over-the-counter medications and herbal preparations, within 1 week prior to first dose of study drug. d) Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of first dose of study drug. e) Use of St. John’s wort (hypericum) within 4 weeks of first dose of study drug. f) Consumption of grapefruit, or seville oranges or any grapefruit or seville orange containing product within 1 week of first dose of study drug and for the duration of the study. g) Use of any agent, within 1 month of dosing, that is known to induce or inhibit drug-metabolizing enzymes (e.g., rifampin, cimetidine, etc.).
6) Prisoners or subjects who are compulsorily detained |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic Measures: Single-dose pharmacokinetic parameters (Cmax, Tmax, AUC(0-T), AUC(INF), and T-HALF) will be derived from plasma concentration versus time after fasting and a light or high-fat meal.
Primary Safety Outcome Measures: Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 3 |