It is a Phase-I, Multiple-dose, two-treatment, three-period, non-randomized fixed sequence, steady state pharmacokinetic interaction study to be conducted in healthy, adult human participants under fasting condition.
- Registration Number
- CTRI/2022/06/043335
- Lead Sponsor
- Hetero Labs Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1.Non-smoking, healthy adult human male or female participants between 18 to 45 years of age
(both inclusive).
2. Having a Body Mass Index (BMI) between 18.5 and 24.9 (both inclusive), calculated as weight in kg per height in meter2.
3. Hemoglobin level greater than or equal to 12.0 gm percent (for male subjects) and greater than or equal to 11.5 gm percent (for female subjects) at the time of screening.
4. Creatinine clearance more than 90 ml per min at screening as per Cockcroft-Gault Equation.
5. Not having any significant disease in medical history or clinically significant abnormal findings during screening, physical examination, laboratory evaluations, 12- lead ECG and X-ray chest (P or A view) recordings.
6. Able to understand and comply with the study procedures, in the opinion of the principal investigator.
7. Literate and able to give voluntary written informed consent for participation in the trial.
8. For Male Subjects, Subjects willing to follow approved birth control methods for the duration of the study as judged by the investigator(s), such as (a double barrier method) condom with spermicide, condom with diaphragm or abstinence. Subjects agree not to donate sperm during the entire course of study.
9. For Female Subjects, Surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject) at least 6 months prior to study participation OR If of child bearing potential 1s willing to use a suitable and effective double barrier contraceptive method (abstinence or double barrier contraception, i.e., condom plus diaphragm, condom plus spermicidal or foam) or intra uterine device during the study and Urine Pregnancy Test at screening and Serum Pregnancy test at screening and prior to check-in of Period-I must be negative.
a) Known hypersensitivity or idiosyncratic reaction to Tenofovir Alafenamide or Dolutegravir or normally used medicines such as anti-histamines, NSAIDs or any of the excipients or related drug.
b) History or presence of any disease or condition which might compromise the haemopoietic, renal,
hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
c) Ingestion of a medicine (any prescribed medications or OTC medications, herbal products including traditional herbal remedies, and homeopathic products, CYP inducers or inhibitors) at any time within 30
days prior to first IMP administration of Period-I and any vaccine (including COVID-19 vaccine) from 30 days prior to first dosing of period-I. In any such case subject selection will be at the discretion of the Principal Investigator.
d) Any history or presence of asthma (including aspirin induced asthma) or nasal polyp or NSAIDs induced urticaria.
e) Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.
f) A recent history of harmful use of alcohol (less than 2 years), i.e. alcohol consumption of more than 14 standard drinks per week for men and more than 07 standard drinks per week for women (A standard drink is defined as 360 ml of beer or 150 mL of wine or 45 mL of 40 percent distilled spirits, such as rum, whisky, brandy etc.) or consumption of alcohol or alcoholic products within 48 hours prior to first IMP administration.
g) Smokers, or who have smoked within last six months prior to start of the study.
h) The presence of clinically significant abnormal laboratory values during screening.
i) History or presence of seizure or psychiatric disorders.
j) A history of difficulty in donating blood.
k) Difficulty in swallowing tablet or capsule.
l) Donation of blood (1 unit or 350 mL) within a period of 90 days prior to the first dose of study
medication.
m) Receipt of an investigational medicinal product or participation in a drug research study within a
period of 90 days prior to the first dose of study medication.
n) A positive hepatitis screen including hepatitis B surface antigen and or HCV antibodies.
o) A positive test result for HIV (1 and or 2) antibody.
p) Alanine aminotransferase (ALT) greater than or equal to 1.5 times upper limit of normal (ULN); Aspartate
aminotransferase (AST) greater than or equal to 1.5 times ULN; Alkaline phosphatase greater than or equal to 1.5 times ULN; Bilirubin greater than 1.5 x ULN (isolated bilirubin greater than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent).
q) Any Grade 2 to 4 laboratory abnormality as per CTCAE grading at Screening, with the exception
of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides) and
ALT or AST (described above), will exclude a participant from the study unless the investigator can
provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A
single repeat of any laboratory abnormality is allowed within a single screening period to
determine eligibility.
r) Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction, sinoatrial pauses,
bundle branch blo
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the effect of HRF-10071 on the steady state pharmacokinetic of Tenofovir Alafenamide/Tenofovir/Dolutegravir in healthy, adult human participants under fasting condition. <br/ ><br>To assess the effect of Tenofovir Alafenamide/Tenofovir/Dolutegravir on the steady state pharmacokinetic of HRF-10071 in healthy, adult human participants under fasting condition.Timepoint: Pre-dose On day 1, Day 12, 13 and 14 prior dosing <br/ ><br>Post-dose sample D-14 <br/ ><br>0.250, 0.500, 0.750, 1.000, 1.500, 2.000, 3.000, 4.000, 5.000, 6.000, 8.000, 12.000 and 24.000 hrs <br/ ><br>Post-dose D-14, 1.000, 1.500, 2.000, 3.000, 3.500, 4.000, 4.500, 5.000, 6.000, 8.000, 12.000, 24.000, 48.000 and 72.000 hrs <br/ ><br>Pre-dose-On day 1, 12, 13 and 14 prior dosing <br/ ><br>Post-dose D-14 <br/ ><br>Pre-dose for Tenofovir, Dolutegravir and HRF-10071- On day 1, 12, 13 and 14 prior dosing
- Secondary Outcome Measures
Name Time Method To assess the safety and tolerability of HRF-10071 and Tenofovir alafenamide/Dolutegravir administered alone and when given concurrently in healthy human participants. <br/ ><br>To evaluate steady state pharmacokinetic of HRF-10071 alone and when administered in combination with Tenofovir Alafenamide/Dolutegravir. <br/ ><br>To evaluate steady state pharmacokinetic of Tenofovir Alafenamide/Dolutegravir alone and when administered in combination with HRF-10071.Timepoint: Day 1to14 each period