Adult Lamivudine and Tenofovir Biocomparison Study for Pediatric Fixed Dose Combination Formulation

• Register: EUCTR
• Last refreshed on: 28 November 2016
• Main ID: EUCTR2016-004392-41-Outside-EU/EEA
• Date of registration: 21/11/2016
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Adult Lamivudine and Tenofovir Biocomparison Study for Pediatric Fixed Dose Combination Formulation
• Scientific title: A Study of the Comparative Bioavailability of Two Investigational Pediatric Oral Granule Formulations of Lamivudine and Tenofovir Compared to the Adult Marketed Formulations. Other PIP decision number: P/139/2016 - Adult Lamivudine and Tenofovir Biocomparison Study for Pediatric Fixed dose Combination Formulation
• Target sample size: 24
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004392-41
• 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 Marketed Formulations of Lamividune and Tenofovir Number of treatment arms in the trial: 12
• 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) Females who participate in this study will be of childbearing or non-childbearing potential:
• Childbearing potential: Physically capable of becoming pregnant
• Non-childbearing potential: Surgically sterile (i.e., both ovaries removed, uterus removed or bilateral tubal ligation); and/or Postmenopausal (no menstrual period for at least 12 consecutive months without any other medical cause).
4) Willing to use acceptable, effective methods of contraception.
5) Subjects provide written informed consent/assent for the trial, including for Future Biomedical Research.
6) Able to drink approximately 480 mL of water and 50 mL of whole milk in 30 minutes.
7) Able to tolerate venipuncture.
8) Be informed of the nature of the study and give written consent prior to any study procedure.

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, 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 lamivudine or tenofovir 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) Presence of mouth piercings (object or hole), presence of non-removable dentures and orthodontic appliances (e.g., braces, retainers), or any other alteration to the mouth that may be deemed by the Investigator to 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 or presence of clinically significant gastrointestinal disease.
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 (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) or urine cotinine.
16) Difficulty fasting or consuming standard meals.
17) Use of tobacco or nicotine-containing products within 6 months prior to the first drug administration.
18) Females who:
• Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within 6 months prior to the first drug administration;
• 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.
19) Donation or loss of whole blood (including clinical trials):
• =50 mL and <500 mL within 30 days prior to the first drug
administration;
• =500 mL within 56 days prior to the first drug administration.
20) Participation in a clinical trial that involved administration of an investigational medicinal product within 30 days prior to the first drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results.
21) On a special diet within 30 days prior to drug administration (e.g., liquid, protein,

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)

Trade Name: 3TC® (Lamivudine)
Product Name: Lamivudine
Pharmaceutical Form: Tablet
INN or Proposed INN: LAMIVUDINE
CAS Number: 134678-17-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Product Name: Lamivudine - uncoated granules - 300 mg
Pharmaceutical Form: Granules
INN or Proposed INN: LAMIVUDINE
CAS Number: 134678-17-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Lamivudine - coated granules -300 mg
Pharmaceutical Form: Granules
INN or Proposed INN: LAMIVUDINE
CAS Number: 134678-17-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: VIREAD® (tenofovir disoproxil fumarate)
Product Name: VIREAD
Pharmaceutical Form: Tablet
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Product Name: tenofovir disoproxil fumarate - uncoated granules - 300 mg
Pharmaceutical Form: Granules
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: tenofovir disoproxil fumarate - coated granules - 300 mg
Pharmaceutical Form: Granules
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: Not applicable

Main Objective: To evaluate the comparative bioavailability of:
1.lamivudine 300mg:
a. adult marketed tablets to the investigational oral pediatric uncoated/coated granules-fasted conditions
b.investigational oral pediatric uncoated granules-fasted conditions, to the investigational oral pediatric uncoated granules-fasted conditions+vanilla pudding/applesauce
c.investigational oral pediatric coated granules-fasted conditions, to the investigational oral pediatric coated granules-fasted conditions+vanilla pudding/applesauce
2.tenofovir 300mg:
a.adult marketed tablets to the investigational oral pediatric uncoated/coated granules - under fasted conditions
b.investigational oral pediatric uncoated granules-fasted conditions, to the investigational oral pediatric uncoated granules-fasted conditions+vanilla pudding/applesauce
c.investigational oral pediatric coated granules-fasted conditions, to the investigational oral pediatric coated granules - fasted conditions+vanilla pudding/applesauce

Timepoint(s) of evaluation of this end point: In each period, prior to (0-hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours after first drug administration.

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

Secondary Outcome(s)

Secondary end point(s): not applicable

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

Secondary ID(s)

2017-4208

MK-1439A-054

Source(s) of Monetary Support

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