E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV – Human Immunodeficiency Virus |
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E.1.1.1 | Medical condition in easily understood language |
HIV – Human Immunodeficiency Virus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 evaluate the comparative bioavailability of a single-dose of the investigational oral pediatric minitablet formulation of MK-1439, 0.8 mg [100 mg total dose] compared to the adult formulation of MK-1439 tablets, 100 mg in healthy adult male and female subjects under fasted conditions. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Non-tobacco using males and non-pregnant females, 18-55 years of age, inclusive.
2. A body mass index (BMI) of 18-30 kg/m² inclusive as calculated according to Novum Standard Operating Procedures.
3. Alkaline phosphatase, alanine transaminase (ALT/SGPT), aspartate transaminase (AST/SGOT), and bilirubin (total and direct) are below the upper limit of normal based on the clinically acceptable normal range; obtained from the clinical laboratory tests performed at screening.
4. If female and of childbearing potential, prepared to abstain from sexual intercourse, or have used and agree to continue to use a reliable method of contraception (e.g., hormonal contraceptives, condom with spermicide, IUD) for at least 30 days before initial dosing and throughout the duration of the study.
5. Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening.
6. Able to consume the entire contents of a 6 oz. container of lowfat vanilla or french vanilla yogurt (e.g., Stonyfield Organic™ Smooth & Creamy lowfat french vanilla yogurt) within 10 minutes, at screening.
7. Signed and dated written informed consent form for the trial, which meets all criteria of current ICH, FDA and state regulations.
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E.4 | Principal exclusion criteria |
1. Females who are pregnant, lactating or likely to become pregnant during the study.
2. History of allergy or sensitivity to MK-1439 or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of study.
3. Lactose intolerant.
4. Significant history or current evidence of chronic infectious disease, system disorders, organ dysfunction, especially cardiovascular disorders (angina, heart failure, irregular heartbeats, heart attack, hypertension, hypotension), stroke, renal or hepatic disorder, diabetes or bleeding disorders.
5. Clinically significant history or presence of gastrointestinal disease or malabsorption within the last year, as determined by the Investigator.
6. Presence of a medical condition requiring regular treatment with prescription drugs (except hormonal contraceptives).
7. History of psychiatric disorders occurring within the last two years that required the subject to be hospitalized or treated with medication.
8. Use of pharmacologic agents known to significantly induce or inhibit drug-metabolizing enzymes (e.g., CYP3A4) within 30 days before initial dosing.
9. Receipt of any drug as part of a research study within 30 days before initial dosing.
10. Drug or alcohol addiction requiring treatment in the past 12 months.
11. History of excessive alcohol consumption (on average more than 14 units of alcohol/week) during the past 12 months.
12. Donation or significant loss of whole blood (480 mL or more) within 30 days or plasma within 14 days before initial dosing.
13. Positive test for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
14. Positive test results for drugs of abuse at screening.
15. If female, has a positive serum pregnancy test at screening.
16. Use of tobacco products, or other nicotine containing products such as patches or gum within 90 days before initial dosing.
17. Difficulty fasting, eating yogurt, or eating the standard meals that will be provided during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The following PK parameters will be estimated for MK-1439:
AUC0-last: The area under the analyte concentration versus time curve, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear up/log down trapezoidal method
AUC0-inf: The area under the analyte concentration versus time curve from time zero to infinity. AUC0-inf = AUC0-last + Cp/Kel, where Cp is the predicted analyte concentration at the time of the last measurable analyte concentration
C24hr: The concentration of the analyte in plasma at 24 hours post administration
Cmax: Maximum measured analyte concentration over the sampling period
Tmax: Time of the maximum measured analyte concentration over the sampling period
Kel: The apparent first-order elimination rate constant
T½: The apparent elimination half-life
CL/F: Apparent total plasma clearance of drug after oral administration (CL/F = Dose/AUC0-inf)
Vd/F: Apparent volume of distribution during the terminal phase after oral drug administration (Vd/F = Dose/[AUC0-inf*Kel])
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 48, and 72 hours post-dose |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Comparative Bioavailability |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
MK-1439 Adult Formulation Tablet |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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.8.9.2 | In all countries concerned by the trial days | 16 |