A Study of the Comparative Bioavailability of Two Second-Generation Investigational Pediatric Oral Granule Formulations of MK-1439 Compared to the Adult Formulation

• Register: EUCTR
• Last refreshed on: 21 November 2016
• Main ID: EUCTR2016-004656-30-Outside-EU/EEA
• Date of registration: 16/11/2016
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: A Study of the Comparative Bioavailability of Two Second-Generation Investigational Pediatric Oral Granule Formulations of MK-1439 Compared to the Adult Formulation
• Scientific title: A Study of the Comparative Bioavailability of Two Second-Generation Investigational Pediatric Oral Granule Formulations of MK-1439 Compared to the Adult Formulation. Additional PIP decision number: P/139/2016 - MK-1439 Mini-Tab Study
• Target sample size: 24
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004656-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: adult formulation tablets of MK-1439 Number of treatment arms in the trial: 7
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada

Contacts

• Name: Martin Otto Behm
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Martin Otto Behm
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1) Healthy, non-smoking, male and female subjects, from 18 to 55 years of age.
2) BMI =19.0 and =30.0 kg/m2.
3) No clinically significant findings in vital signs measurements.
4) No clinically significant findings in a 12-lead electrocardiogram (ECG).
5) No clinically significant abnormal laboratory values.
6) Have no significant diseases.
7) Willing to use an acceptable, effective method of contraception.
8) Subjects provide written informed consent/assent for the trial, including for Future Biomedical Research.
9) Have no clinically significant findings from a physical examination.
10) Must be able to consume pudding and applesauce and be able to consume a serving of each, without chewing, in 10 minutes or less at screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) Known history or presence of clinically significant neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, gastrointestinal, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
2) Known or suspected carcinoma.
3) Known history or presence of hypersensitivity or idiosyncratic reaction to MK-1439 or any other drug substances with similar activity.
4) History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
5) Mentally or legally incapacitated, has significant emotional problems at the time of screening or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 years. Subjects who have had situational depression may be enrolled in the study at the discretion of the investigator.
6) Subjects with permanent or removable mouth piercing or non-removable mouth piercings, dentures, braces, dental appliances, or any other alteration to the mouth that may compromise drug delivery.
7) History of any surgery on the oral cavity or throat in the past year.
8) Known history or presence of galactose or fructose intolerance, sucraseisomaltase insufficiency, Lapp lactase insufficiency, galactosemia, or glucose-galactose malabsorption syndrome.
9) Presence of hepatic or renal dysfunction.
10) Estimated creatinine clearance of =80 mL/min based on the Cockcroft- Gault equation.
11) History of malabsorption within the last year.
12) Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption.
13) History of drug or alcohol addiction requiring treatment.
14) Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
15) Positive test result for urine drugs of abuse (cannabinoids, opiates, amphetamines, cocaine, phencyclidine, tricyclic antidepressants, barbiturates, methadone, and benzodiazepines) or urine cotinine.
16) Difficulty fasting or consuming standard meals.
17) Does not tolerate venipuncture.
18) Use of tobacco or nicotine-containing products within 6 months prior to drug administration.
19) Females who:
• Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within 6 months prior to dosing;
• Have discontinued or changed the use of oral or patch hormonal contraceptives within 1 month prior to drug administration;
• Are pregnant (serum hCG consistent with pregnancy); or
• Are lactating.
20) Donation or loss of whole blood (including clinical trials):
• =50 mL and <500 mL within 30 days prior to drug administration;
• =500 mL within 56 days prior to drug administration.
21) Participated in a clinical trial that involved administration of an investigational medicinal product within 30 days prior to drug administration, or recently participated in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results.
22) On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet).
23) Have had a tattoo or body piercing within 30 days prior to drug administration.
24) Use of any enzyme-modifyi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HIV-1 Infection
MedDRA version: 19.0 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Doravirine
Product Code: MK-1439
Pharmaceutical Form: Tablet
INN or Proposed INN: Doravirine
Current Sponsor code: MK-1439
Other descriptive name: MK-1439
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: Doravirine - MK-1439 - uncoated granules - 100 mg
Product Code: MK-1439
Pharmaceutical Form: Granules
INN or Proposed INN: Doravirine
Current Sponsor code: MK-1439
Other descriptive name: MK-1439
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.8-

Product Name: Doravirine - MK-1439 - coated granules - 100 mg
Product Code: MK-1439
Pharmaceutical Form: Granules
INN or Proposed INN: Doravirine
Current Sponsor code: MK-1439
Other descriptive name: MK-1439
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.8-

Primary Outcome(s)

Primary end point(s): The following pharmacokinetic parameters will be estimated using a non-compartmental approach for MK-1439: C24, Cmax, Tmax, AUC0-last, AUC0-inf, t1/2, ?z, CL/F, and Vz/F

Main Objective: 1.To evaluate the comparative bioavailability of the MK-1439 100 mg adult formulation tablets under fasting conditions to MK-1439 100 mg investigational oral pediatric uncoated and coated granules, 0.8 mg per granule [100 mg total dose], under fasting conditions
2.To evaluate the comparative bioavailability of the MK- 1439 100 mg investigational oral pediatric uncoated granule formulation, 0.8 mg per granule [100 mg total dose], under fasting conditions to MK-1439 100 mg investigational oral pediatric uncoated granules, 0.8 mg per granule [100 mg total dose], under fasting conditions, when given with vanilla pudding or applesauce
3.To evaluate the comparative bioavailability of the MK- 1439 100 mg investigational oral pediatric coated granules, 0.8 mg per granule [100 mg total dose], under fasting conditions to MK-1439 100 mg investigational oral pediatric coated granules, 0.8 mg per granule [100 mg total dose], under fasting conditions when given with vanilla pudding or applesauce

Timepoint(s) of evaluation of this end point: Prior to dosing (0-hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose.

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

MK-1439-052

2016-4089

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.