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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03537404
Recruitment Status : Completed
First Posted : May 25, 2018
Results First Posted : February 19, 2019
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
Almedis
Information provided by (Responsible Party):
R-Pharm

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Narlaprevir Drug: Ritonavir Drug: Tenofovir Disoproxil Fumarate Drug: Raltegravir Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs
Actual Study Start Date : April 24, 2017
Actual Primary Completion Date : June 24, 2017
Actual Study Completion Date : June 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Active Comparator: Treatment A (Part 1/ Part 2)
Narlaprevir 200 mg once daily with Ritonavir 100 mg once daily for 5 days
Drug: Narlaprevir
100 mg, film-coated tablets, taken as 200 mg per os daily
Other Name: Arlansa

Drug: Ritonavir
100 mg, film-coated tablets, taken as 100 mg per os daily
Other Name: Norvir

Active Comparator: Treatment B (Part 1)
Tenofovir disoproxil fumarate 300 mg once daily for 5 days
Drug: Tenofovir Disoproxil Fumarate
300 mg, film-coated tablets, taken as 300 mg per os daily
Other Names:
  • Tenofovir-TL
  • Viread

Active Comparator: Treatment B (Part 2)
Raltegravir 400 mg twice daily for 5 days
Drug: Raltegravir
400 mg, film-coated tablets, taken as 400 mg per os daily
Other Name: Isentress

Experimental: 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
Drug: Narlaprevir
100 mg, film-coated tablets, taken as 200 mg per os daily
Other Name: Arlansa

Drug: Ritonavir
100 mg, film-coated tablets, taken as 100 mg per os daily
Other Name: Norvir

Drug: Tenofovir Disoproxil Fumarate
300 mg, film-coated tablets, taken as 300 mg per os daily
Other Names:
  • Tenofovir-TL
  • Viread

Experimental: 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
Drug: Narlaprevir
100 mg, film-coated tablets, taken as 200 mg per os daily
Other Name: Arlansa

Drug: Ritonavir
100 mg, film-coated tablets, taken as 100 mg per os daily
Other Name: Norvir

Drug: Raltegravir
400 mg, film-coated tablets, taken as 400 mg per os daily
Other Name: Isentress




Primary Outcome Measures :
  1. Cmax of Narlaprevir [ Time Frame: 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) ]
    Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study

  2. AUCtau of Narlaprevir [ Time Frame: 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) ]
    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

  3. Cmax of Tenofovir [ Time Frame: 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) ]
    Maximum observed Concentration of Tenofovir at Day 5 of treatment B and C of Part 1 of the study

  4. AUCtau of Tenofovir [ Time Frame: 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) ]
    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

  5. Cmax of Raltegravir [ Time Frame: 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) ]
    Maximum observed Concentration of Raltegravir at Day 5 of treatment B and C of Part 2 of the study

  6. AUCtau of Raltegravir [ Time Frame: 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) ]
    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


Secondary Outcome Measures :
  1. Number of Patients With Adverse Events [ Time Frame: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study ]
  2. Number of Patients With Changes in Vital Signs [ Time Frame: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study ]
    There were no subjects with abnormal changes in vital signs

  3. Number of Patients With Abnormal Laboratory Values [ Time Frame: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study ]
  4. Number of Patients With Abnormal ECG Changes [ Time Frame: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study ]
    There were no subjects with abnormal ECG changes during the study



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03537404


Locations
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Russian Federation
Clinic "Bessalar" JSC
Moscow, Russian Federation
Sponsors and Collaborators
R-Pharm
Almedis
Investigators
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Study Director: Mikhail Samsonov R-Pharm
  Study Documents (Full-Text)

Documents provided by R-Pharm:

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Responsible Party: R-Pharm
ClinicalTrials.gov Identifier: NCT03537404     History of Changes
Other Study ID Numbers: CJ05013019
First Posted: May 25, 2018    Key Record Dates
Results First Posted: February 19, 2019
Last Update Posted: February 19, 2019
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by R-Pharm:
hepatitis C
chronic
pharmacokinetics
HIV
coinfection
concomitant therapy
Additional relevant MeSH terms:
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Ritonavir
Tenofovir
Raltegravir Potassium
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors