A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs

NCT ID: NCT03537404

Last Updated: 2019-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-24
• Study Completion Date: 2017-06-30

Brief Summary

The study purpose is to evaluate the potential for a pharmacokinetic drug-drug interaction, safety and tolerability when Narlaprevir, Ritonavir (used as a metabolic inhibitor) and Tenofovir disoproxil fumarate (part 1) and Narlaprevir, Ritonavir and Raltegravir (part 2) are administered in combination to healthy volunteers.

Detailed Description

The current study includes 2 parts, as the following drugs may be used concomitantly to treat hepatitis C virus (HCV)/HIV coinfection:

• Part 1 of the study is being conducted to evaluate the pharmacokinetic effect of coadministration of narlaprevir with ritonavir and tenofovir disoproxil fumarate.
• Part 2 of the study is being conducted to evaluate the pharmacokinetic effect of coadministration of narlaprevir/ritonavir and raltegravir.

Each part of the study is designed as a randomized 3-period crossover study and will assess if there is any effect of tenofovir disoproxil fumarate or raltegravir on the pharmacokinetics of narlaprevir and vice versa.

Subjects will be screened within 28 days before dosing in this multi-part study. All subjects eligible for protocol criteria will be randomized 1:1:1 to receive one of the following treatment sequences: A/B/C, or B/C/A, or C/A/B. Every subject will receive only one treatment (A or B or C) in one Period. Subjects will be confined to the study center throughout treatment in each period. Following completion of study procedures for each treatment period, subjects will be released from the clinic. After a 7-14 (maximum) days interval between dosing, subjects will return to start hospitalization for the next treatment period. Subjects will be discharged from the study upon completion of all study related procedures in Period 3. Phone call will be conducted after 5-7 days of follow-up period to assess safety data.

This drug interaction study is designed to investigate pharmacokinetic drug-drug interactions between Narlaprevir coadministered with Ritonavir and antiretroviral drugs (Tenofovir disoproxil fumarate and Raltegravir) for labeling and clinical dosing guidance purposes.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment A (Part 1/ Part 2)

Narlaprevir 200 mg once daily with Ritonavir 100 mg once daily for 5 days

Group Type: ACTIVE_COMPARATOR

Narlaprevir

Intervention Type: DRUG

100 mg, film-coated tablets, taken as 200 mg per os daily

Ritonavir

Intervention Type: DRUG

100 mg, film-coated tablets, taken as 100 mg per os daily

Treatment B (Part 1)

Tenofovir disoproxil fumarate 300 mg once daily for 5 days

Group Type: ACTIVE_COMPARATOR

Tenofovir Disoproxil Fumarate

Intervention Type: DRUG

300 mg, film-coated tablets, taken as 300 mg per os daily

Treatment B (Part 2)

Raltegravir 400 mg twice daily for 5 days

Group Type: ACTIVE_COMPARATOR

Raltegravir

Intervention Type: DRUG

400 mg, film-coated tablets, taken as 400 mg per os daily

Treatment C (Part 1)

Narlaprevir 200 mg once daily coadministered with ritonavir 100 mg once daily and Tenofovir disoproxil fumarate 300 mg once daily for 5 days

Group Type: EXPERIMENTAL

Narlaprevir

Intervention Type: DRUG

100 mg, film-coated tablets, taken as 200 mg per os daily

Ritonavir

Intervention Type: DRUG

100 mg, film-coated tablets, taken as 100 mg per os daily

Tenofovir Disoproxil Fumarate

Intervention Type: DRUG

300 mg, film-coated tablets, taken as 300 mg per os daily

Treatment C (Part 2)

Narlaprevir 200 mg once daily coadministered with ritonavir 100 mg once daily and 400 mg raltegravir twice daily for 5 days

Group Type: EXPERIMENTAL

Narlaprevir

Intervention Type: DRUG

100 mg, film-coated tablets, taken as 200 mg per os daily

Ritonavir

Intervention Type: DRUG

100 mg, film-coated tablets, taken as 100 mg per os daily

Raltegravir

Intervention Type: DRUG

400 mg, film-coated tablets, taken as 400 mg per os daily

Interventions

Narlaprevir

100 mg, film-coated tablets, taken as 200 mg per os daily

Intervention Type: DRUG

Ritonavir

100 mg, film-coated tablets, taken as 100 mg per os daily

Intervention Type: DRUG

Tenofovir Disoproxil Fumarate

300 mg, film-coated tablets, taken as 300 mg per os daily

Intervention Type: DRUG

Raltegravir

400 mg, film-coated tablets, taken as 400 mg per os daily

Intervention Type: DRUG

Other Intervention Names

Arlansa; Norvir; Tenofovir-TL; Viread; Isentress

Eligibility Criteria

Inclusion Criteria

• Subjects must be willing to give written informed consent for the trial and able to adhere to dose and visit schedules.
• Subjects having a Body Mass Index (BMI) between 18,5 and 30 kg/m^2, inclusive.
• Subjects should diagnosed as "healthy": no pathology of the gastrointestinal tract, liver, kidneys, cardiovascular system, central nervous system (previously carried out by standard clinical and lab tests which did not reveal the presence of any diseases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must not exceed the normal range; QT interval calculated by Bazett's formula (QTcB) for men should be ≤ 450 ms and ≤ 470 ms for women, the interval PR should be ≤ 200 ms).
• Vital sign measurements (taken after ~3 minutes in a supine or sitting position) must be within the following ranges:

1. systolic blood pressure, 100 - 130 mm Hg;

2. diastolic blood pressure, 60 -90 mm Hg;

3. pulse rate, 60-80 bpm.

• Female subjects must be:

1. postmenopausal (defined as 12 months with no menses; age > 40 years and with a follicle-stimulating hormone (FSH) level of >40 u/mL);

2. surgically sterilized at least 3 months prior to baseline (e.g., documented hysterectomy or tubal ligation).

• Men must agree to use a medically accepted method of contraception (condom and spermicide) during the trial and for 3 months after stopping the medication.

Exclusion Criteria

• Females with childbearing potential.
• Subjects who, in the opinion of the investigator, will not be able to participate optimally in the study.
• Positive results for hepatitis B surface antigen, hepatitis C antibodies or HIV, positive RW results.
• Allergic reactions in history.
• Intolerance to medication.
• Chronic disease of cardiovascular, bronchopulmonary, and/or neuroendocrine systems, gastrointestinal, liver, pancreas, kidney and/or blood disease.
• History or presence of impaired renal function, lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
• History of urinary obstruction or difficulty in voiding.
• Gastrointestinal surgery in history (except of appendectomy).
• Acute infections less than 4 weeks before participation in the study.
• Subjects with a medical history of osteopenia and/or osteoporosis.
• Regular administration of any medicines less than 4 weeks before participation in the study.
• Administration of medicines with marked influence on hemodynamics, liver function et al (barbiturates, omeprazole, cimetidine et al) less than 30 days before participation in the study.
• Blood donation (450 ml or more of blood or plasma) less than 2 months before participation in the study.
• Intake of more than 10 units of alcohol in a week (1 unit of alcohol is equal to 0.5 L of beer, 200 mL of wine or 50 mL of spirits) or history of drug abuse or alcoholism.
• Smoking of more than 10 cigarettes or equivalent tobacco use per day.
• Participation in phase 1 clinical trial less than 3 months before participation in the study.
• Positive screen for drugs abuse and drugs use.
• Subjects with a medical history of psychiatric or personality disorders that in the opinion of the investigator and sponsor, affects the subject's ability to participate in the trial.
• Subjects who are part of the study staff personnel or family members of the study staff personnel.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Almedis

INDUSTRY

Sponsor Role: collaborator

R-Pharm

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikhail Samsonov

Role: STUDY_DIRECTOR

R-Pharm

Locations

Clinic "Bessalar" JSC

Moscow, , Russia

Countries

Russia

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CJ05013019

Identifier Type: -

Identifier Source: org_study_id