CompletedNCT03537404Updated Feb 19, 2019Results posted

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

A Phase 1 interventional study of Narlaprevir and Ritonavir in Healthy, sponsored by R-Pharm. Completed at 1 site in Russian Federation. Open to participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-02-19.

Sponsored by R-Pharm · Phase 1, Interventional, and Treatment

From the registry’s dates

Registered 1 year after the study started (first participant enrolled Apr 2017, registered May 2018).

Phase: Phase 1
Study type: Interventional
Enrollment: 36
Allocation: Randomized
Ages: 21 Years to 55 Years
Sex: All

Study 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.

Read the 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 studied

Healthy

Keywords

hepatitis C
chronic
pharmacokinetics
HIV
coinfection
concomitant therapy

In context

Lead sponsor

R-Pharm is the lead sponsor of 55 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 21 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility 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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 36 participants (actual)

Study arms

Active comparator
Treatment A (Part 1/ Part 2)
Narlaprevir 200 mg once daily with Ritonavir 100 mg once daily for 5 days
Drug: Narlaprevir · Drug: Ritonavir
Active comparator
Treatment B (Part 1)
Tenofovir disoproxil fumarate 300 mg once daily for 5 days
Drug: Tenofovir Disoproxil Fumarate
Active comparator
Treatment B (Part 2)
Raltegravir 400 mg twice daily for 5 days
Drug: Raltegravir
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 · Drug: Ritonavir · Drug: Tenofovir Disoproxil Fumarate
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 · Drug: Ritonavir · Drug: Raltegravir

Interventions

DrugNarlaprevir
100 mg, film-coated tablets, taken as 200 mg per os daily
Also known as: Arlansa
DrugRitonavir
100 mg, film-coated tablets, taken as 100 mg per os daily
Also known as: Norvir
DrugTenofovir Disoproxil Fumarate
300 mg, film-coated tablets, taken as 300 mg per os daily
Also known as: Tenofovir-TL, Viread
DrugRaltegravir
400 mg, film-coated tablets, taken as 400 mg per os daily
Also known as: Isentress

What researchers measure

Primary outcomes

Cmax of Narlaprevir
Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study
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)
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
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)
Cmax of Tenofovir
Maximum observed Concentration of Tenofovir at Day 5 of treatment B and C of Part 1 of the study
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)
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
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)
Cmax of Raltegravir
Maximum observed Concentration of Raltegravir at Day 5 of treatment B and C of Part 2 of the study
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)
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
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)

Secondary outcomes

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
Number of Patients With Changes in Vital Signs
There were no subjects with abnormal 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
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
Number of Patients With Abnormal ECG Changes
There were no subjects with abnormal ECG changes during the study
Time frame: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Results

Posted Feb 19, 2019

Participant flow

Healthy adult volunteers were recruited for all Parts of the study in one clinical site (Bessalar clinic) in Moscow between April and June 2017. 36 subjects were randomized so that 18 subjects participated in each Part of the study (6 subjects in each treatment group of each Part).

First Intervention (A or B or C)

Participant flow — First Intervention (A or B or C)
Milestone	Part 1	Part 2
Started	18	18
Completed	18	18
Not completed	0	0

First Washout Period (8 Days)

Participant flow — First Washout Period (8 Days)
Milestone	Part 1	Part 2
Started	18	18
Completed	18	18
Not completed	0	0

Second Intervention (A or B or C)

Participant flow — Second Intervention (A or B or C)
Milestone	Part 1	Part 2
Started	18	18
Completed	18	18
Not completed	0	0

Second Washout Period (8 Days)

Participant flow — Second Washout Period (8 Days)
Milestone	Part 1	Part 2
Started	18	18
Completed	18	18
Not completed	0	0

Third Intervention (A or B or C)

Participant flow — Third Intervention (A or B or C)
Milestone	Part 1	Part 2
Started	18	18
Completed	18	18
Not completed	0	0

Outcome measures

PrimaryCmax of Narlaprevir

Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study

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)
Reported as:: Geometric mean · ng/ml

Cmax of Narlaprevir
ng/ml	Treatment A (Part 1)	Treatment C (Part 1)	Treatment A (Part 2)	Treatment C (Part 2)
Cmax of Narlaprevir	2130.2742 (1817.4088 to 2731.8348)	2172.233 (1895.673 to 2726.557)	2946.131 (2617.485 to 3799.642)	2880.612 (2412.858 to 4121.871)

Statistical analysis

Treatment A (Part 1) vs Treatment C (Part 1) · Geometric mean ratio: 0.020 · 90% CI -0.103 to 0.142Cmax parameters were logarithmically transformed
Treatment A (Part 2) vs Treatment C (Part 2) · Geometric mean ratio: -0.022 · 90% CI -0.220 to 0.175Cmax parameters were logarithmically transformed

PrimaryAUCtau 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

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)
Reported as:: Geometric mean · ng*h/ml

AUCtau of Narlaprevir
ng*h/ml	Treatment A (Part 1)	Treatment C (Part 1)	Treatment A (Part 2)	Treatment C (Part 2)
AUCtau of Narlaprevir	20504.31 (18265.63 to 24328.95)	21366.2 (18664.1 to 26481.9)	26199.19 (23136.15 to 33132.53)	24458.48 (20738.76 to 33597.42)

Statistical analysis

Treatment A (Part 1) vs Treatment C (Part 1) · Geometric mean ratio: 0.041 · 90% CI -0.075 to 0.157AUCtau parameters were logarithmically transformed.
Treatment A (Part 2) vs Treatment C (Part 2) · Geometric mean ratio: -0.069 · 90% CI -0.201 to 0.064AUCtau parameters were logarithmically transformed

PrimaryCmax of Tenofovir

Maximum observed Concentration of Tenofovir at Day 5 of treatment B and C of Part 1 of the study

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)
Reported as:: Geometric mean · ng/ml

Cmax of Tenofovir
ng/ml	Treatment B (Part 1)	Treatment C (Part 1)
Cmax of Tenofovir	263.037 (233.126 to 313.318)	344.796 (302.457 to 415.092)

Statistical analysis

Treatment B (Part 1) vs Treatment C (Part 1) · Geometric mean ratio: 0.271 · 90% CI 0.159 to 0.383Cmax parameters were logarithmically transformed

PrimaryAUCtau 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

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)
Reported as:: Geometric mean · ng*h/ml

AUCtau of Tenofovir
ng*h/ml	Treatment B (Part 1)	Treatment C (Part 1)
AUCtau of Tenofovir	2599.95 (2325.72 to 3043.02)	2799.72 (2536.67 to 3205.65)

Statistical analysis

Treatment B (Part 1) vs Treatment C (Part 1) · Geometric mean ratio: 0.074 · 90% CI 0.016 to 0.132AUCtau parameters were logarithmically transformed

PrimaryCmax of Raltegravir

Maximum observed Concentration of Raltegravir at Day 5 of treatment B and C of Part 2 of the study

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)
Reported as:: Geometric mean · ng/ml

Cmax of Raltegravir
ng/ml	Treatment B (Part 2)	Treatment C (Part 2)
Cmax of Raltegravir	830.204 (520.042 to 2758.109)	715.726 (136.163 to 2396.130)

Statistical analysis

Treatment B (Part 2) vs Treatment C (Part 2) · Geometric mean ratio: -0.148 · 90% CI -0.450 to 0.153Cmax parameters were logarithmically transformed

PrimaryAUCtau 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

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)
Reported as:: Geometric mean · ng*h/ml

AUCtau of Raltegravir
ng*h/ml	Treatment B (Part 2)	Treatment C (Part 2)
AUCtau of Raltegravir	2912.45 (1983.01 to 8451.44)	2653.65 (1033.88 to 6964.58)

Statistical analysis

Treatment B (Part 2) vs Treatment C (Part 2) · Geometric mean ratio: -0.093 · 90% CI -0.354 to 0.168AUCtau parameters were logarithmically transformed

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Patients With Adverse Events
Participants	Treatment A (Part 1)	Treatment B (Part 1)	Treatment C (Part 1)	Treatment A (Part 2)	Treatment B (Part 2)	Treatment C (Part 2)
Number of Patients With Adverse Events	1	0	4	0	0	1

SecondaryNumber of Patients With Changes in Vital Signs

There were no subjects with abnormal 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
Reported as:: Count of participants · Participants

Number of Patients With Changes in Vital Signs
Participants	Treatment A (Part 1)	Treatment B (Part 1)	Treatment C (Part 1)	Treatment A (Part 2)	Treatment B (Part 2)	Treatment C (Part 2)
Number of Patients With Changes in Vital Signs	0	0	0	0	0	0

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Patients With Abnormal Laboratory Values
Participants	Treatment A (Part 1)	Treatment B (Part 1)	Treatment C (Part 1)
Part 1	0	0	2
Part 2	0	0	1

SecondaryNumber of Patients With Abnormal ECG Changes

There were no subjects with abnormal ECG changes during the study

Time frame:: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Reported as:: Count of participants · Participants

Number of Patients With Abnormal ECG Changes
Participants	Treatment A (Part 1/Part 2)	Treatment B (Part 1/Part 2)	Treatment C (Part 1/Part 2)
Part 1	0	0	0
Part 2	0	0	0

Adverse events

Collected over Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Treatment A (Part 1)	0/18 (0%)	0/18 (0%)	1/18 (5.6%)
Treatment B (Part 1)	0/18 (0%)	0/18 (0%)	0/18 (0%)
Treatment C (Part 1)	0/18 (0%)	0/18 (0%)	4/18 (22.2%)
Treatment A (Part 2)	0/18 (0%)	0/18 (0%)	0/18 (0%)
Treatment B (Part 2)	0/18 (0%)	0/18 (0%)	0/18 (0%)
Treatment C (Part 2)	0/18 (0%)	0/18 (0%)	1/18 (5.6%)

Most frequent other events

Most frequent other events
Event	Treatment A (Part 1)	Treatment B (Part 1)	Treatment C (Part 1)	Treatment A (Part 2)	Treatment B (Part 2)	Treatment C (Part 2)
Alanine Aminotransferase IncreasedInvestigations	0/18	0/18	1/18	0/18	0/18	1/18
Blood Lactate Dehydrogenase DecreasedInvestigations	0/18	0/18	1/18	0/18	0/18	0/18
HeadacheNervous system disorders	1/18	0/18	1/18	0/18	0/18	0/18
DiarrhoeaGastrointestinal disorders	0/18	0/18	1/18	0/18	0/18	0/18
Gamma-Glutamyltransferase IncreasedInvestigations	0/18	0/18	0/18	0/18	0/18	1/18

Baseline characteristics

All 36 subjects randomized to study treatment and received at least one dose of study drug (Safety Population).

Age, Continuous
Age, Continuous(years)	Sequence A/B/C	Sequence B/C/A	Sequence C/A/B	Total
Part 1	24.3 ± 1.75	38.3 ± 8.26	29.7 ± 1.86	30.8 ± 7.57
Part 2	24.3 ± 4.03	38.7 ± 4.59	29.5 ± 3.33	30.8 ± 7.17

Sex: Female, Male
Sex: Female, Male(Participants)	Sequence A/B/C	Sequence B/C/A	Sequence C/A/B	Total
Part 1 — Female	0	0	0	0
Part 1 — Male	6	6	6	18
Part 2 — Female	0	0	0	0
Part 2 — Male	6	6	6	18

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Sequence A/B/C	Sequence B/C/A	Sequence C/A/B	Total
Part 1 — White	6	6	5	17
Part 1 — Asian	0	0	1	1
Part 1 — Black	0	0	0	0
Part 1 — Other	0	0	0	0
Part 2 — White	6	5	6	17
Part 2 — Asian	0	1	0	1
Part 2 — Black	0	0	0	0
Part 2 — Other	0	0	0	0

Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m2)	Sequence A/B/C	Sequence B/C/A	Sequence C/A/B	Total
Part 1	23.14 ± 1.287	24.73 ± 3.022	24.20 ± 3.134	24.02 ± 2.554
Part 2	24.26 ± 4.132	25.40 ± 2.732	25.63 ± 3.408	25.10 ± 3.319

Study locations

1 site

Clinic "Bessalar" JSC
Moscow, Russian Federation

References and documents

Study documents

Protocol and statistical analysis plan · Feb 20, 2017

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03537404
Lead sponsor: R-Pharm
Collaborators: Almedis
Responsible party: Sponsor
First posted: May 25, 2018
Start date: Apr 24, 2017
Primary completion: Jun 24, 2017
Completion: Jun 30, 2017
Results posted: Feb 19, 2019
Last update: Feb 19, 2019

Study contacts

Mikhail Samsonov

study director · R-Pharm

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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