| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 |
|
| 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:
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
|
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The Sponsor will conduct Future Biomedical Research on DNA specimens collected for future biomedical research during this clinical trial.
Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented
subjects. The objective of collecting/retaining specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic
treatments. The overarching goal is to use such information to develop safer, more effective drugs/vaccines, and/or to ensure that subjects receive the correct dose of the correct drug/vaccine at the correct time. |
|
| E.3 | Principal 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.
|
|
| E.4 | Principal 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, raw food diet).
22) Have had a tattoo or body piercing within 30 days prior to the first drug administration.
23) Have clinically significant findings in vital signs.
24) Have clinically significant findings in a 12-lead electrocardiogram (ECG).
25) Have clinically significant abnormal laboratory values.
26) Have significant diseases.
27) Have clinically significant findings from a physical examination.
28) Use of any enzyme-modifying drugs known to induce/inhibit hepatic drug metabolism or alter gastrointestinal pH/movement (e.g., omeprazole, ranitidine) within 30 days prior to the first drug administration.
|
|
| E.5 End points |
| E.5.1 | 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, λz, CL/F, and Vz/F |
|
| E.5.1.1 | 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. |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 |
|
| 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 |
| Adult Marketed Formulations of Lamividune and Tenofovir |
|
| E.8.2.4 | Number of treatment arms in the trial | 12 |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
Print
