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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537404
• Other study ID #: CJ05013019
• Status: Completed
• Phase: Phase 1
• Start date: April 24, 2017
• Est. completion date: June 30, 2017

Study information

• Verified date: August 2018
• Source: R-Pharm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 30, 2017
• Est. primary completion date: June 24, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

Inclusion Criteria (the subject must meet all the criteria listed below for entry at baseline and at Days -1 and 1 before each treatment Period):

• 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 (the subject will be excluded from entry if any of the criteria listed below are met at baseline):

• 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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Narlaprevir
100 mg, film-coated tablets, taken as 200 mg per os daily
• Ritonavir
100 mg, film-coated tablets, taken as 100 mg per os daily
• Tenofovir Disoproxil Fumarate
300 mg, film-coated tablets, taken as 300 mg per os daily
• Raltegravir
400 mg, film-coated tablets, taken as 400 mg per os daily

Locations

Country	Name	City	State
Russian Federation	Clinic "Bessalar" JSC	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
R-Pharm	Almedis

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax of Narlaprevir	Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study	Day 5 Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 5 of treatment A and C (Part 1/ Part 2)
Primary	AUCtau of Narlaprevir	Area Under the Concentration-time curve during a dosing interval t at steady state of Narlaprevir at Day 5 of treatment A and C of Part 1/ Part 2 of the study	Day 5 Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 5 of treatment A and C (Part 1/ Part 2)
Primary	Cmax of Tenofovir	Maximum observed Concentration of Tenofovir at Day 5 of treatment B and C of Part 1 of the study	Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 18 and 24 hrs post-dose on Day 5 of treatment B and C (Part 1)
Primary	AUCtau of Tenofovir	Area Under the Concentration-time curve during a dosing interval t at steady state of Tenofovir at Day 5 of treatment B and C of Part 1 of the study	Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 18 and 24 hrs post-dose on Day 5 of treatment B and C (Part 1)
Primary	Cmax of Raltegravir	Maximum observed Concentration of Raltegravir at Day 5 of treatment B and C of Part 2 of the study	Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose of Day 5 of treatment B and C (Part 2)
Primary	AUCtau of Raltegravir	Area Under the Concentration-time curve during a dosing interval t at steady state of Tenofovir at Day 5 of treatment B and C of Part 2 of the study	Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose of Day 5 of treatment B and C (Part 2)
Secondary	Number of Patients With Adverse Events		Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Secondary	Number of Patients With Changes in Vital Signs	There were no subjects with abnormal changes in vital signs	Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Secondary	Number of Patients With Abnormal Laboratory Values		Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Secondary	Number of Patients With Abnormal ECG Changes	There were no subjects with abnormal ECG changes during the study	Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study