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

NCT03537404 | Completed Phase 1 Results

• 1 other identifier: CJ05013019
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

hepatitis C; chronic; pharmacokinetics; HIV; coinfection; concomitant therapy

Outcome Measures

Primary Outcomes (6)

• 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)

• AUCtau of Narlaprevir

  Area Under the Concentration-time curve during a dosing interval τ 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)

• 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)

• AUCtau of Tenofovir

  Area Under the Concentration-time curve during a dosing interval τ 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)

• 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)

• AUCtau of Raltegravir

  Area Under the Concentration-time curve during a dosing interval τ 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 Outcomes (4)

• 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

• Number of Patients With Changes in Vital Signs

  Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

• 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

• Number of Patients With Abnormal ECG Changes

  Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Study Arms (5)

Treatment A (Part 1/ Part 2)

ACTIVE COMPARATOR

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

Drug: Narlaprevir; Drug: Ritonavir

Treatment B (Part 1)

ACTIVE COMPARATOR

Tenofovir disoproxil fumarate 300 mg once daily for 5 days

Drug: Tenofovir Disoproxil Fumarate

Treatment B (Part 2)

ACTIVE COMPARATOR

Raltegravir 400 mg twice daily for 5 days

Drug: Raltegravir

Treatment C (Part 1)

EXPERIMENTAL

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

Drug: Narlaprevir; Drug: Ritonavir; Drug: Tenofovir Disoproxil Fumarate

Treatment C (Part 2)

EXPERIMENTAL

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

Drug: Narlaprevir; Drug: Ritonavir; Drug: Raltegravir

Interventions

Narlaprevir DRUG

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

Also known as: Arlansa

Treatment A (Part 1/ Part 2); Treatment C (Part 1); Treatment C (Part 2)

Ritonavir DRUG

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

Also known as: Norvir

Treatment A (Part 1/ Part 2); Treatment C (Part 1); Treatment C (Part 2)

Tenofovir Disoproxil Fumarate DRUG

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

Also known as: Tenofovir-TL, Viread

Treatment B (Part 1); Treatment C (Part 1)

Raltegravir DRUG

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

Also known as: Isentress

Treatment B (Part 2); Treatment C (Part 2)

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• systolic blood pressure, 100 - 130 mm Hg;
• diastolic blood pressure, 60 -90 mm Hg;
• pulse rate, 60-80 bpm.
• Female subjects must be:
• postmenopausal (defined as 12 months with no menses; age \> 40 years and with a follicle-stimulating hormone (FSH) level of \>40 u/mL);
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• R-Pharm: lead
• Almedis: collaborator

Study Sites (1)

Clinic "Bessalar" JSC

Moscow, Russia

Location

MeSH Terms

Conditions

Hepatitis C; Bronchiolitis Obliterans Syndrome; Coinfection

Interventions

narlaprevir; Ritonavir; Tenofovir; Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrrolidinones; Pyrrolidines

Results Point of Contact

• Title: Emiliya Krasavina, Medical Adviser
• Organization: R-Pharm

krasavina@rpharm.ru

0074959567937

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: May 25, 2018
• Study Start: April 24, 2017
• Primary Completion: June 24, 2017
• Study Completion: June 30, 2017
• Last Updated: February 19, 2019
• Results First Posted: February 19, 2019

Record last verified: 2018-08

Locations

RU (1)