HealthyPhase 1NCT03537404
A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs
A Phase 1 study testing Narlaprevir, Ritonavir and Tenofovir Disoproxil Fumarate in people with Healthy, run by R-Pharm at 1 site in Russia.
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… Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Narlaprevir, Ritonavir and Tenofovir Disoproxil Fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteRussia
- Study dates
- 24 Apr 2017to 30 Jun 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
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:
- 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.
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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NarlaprevirDrug
Also called Arlansa
100 mg, film-coated tablets, taken as 200 mg per os daily
RitonavirDrug
Also called Norvir
100 mg, film-coated tablets, taken as 100 mg per os daily
Tenofovir Disoproxil FumarateDrug
Also called Tenofovir-TL, Viread
300 mg, film-coated tablets, taken as 300 mg per os daily
RaltegravirDrug
Also called Isentress
400 mg, film-coated tablets, taken as 400 mg per os daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment A (Part 1/ Part 2) | Active comparator | Narlaprevir 200 mg once daily with Ritonavir 100 mg once daily for 5 days Receives: Drug: Narlaprevir; Drug: Ritonavir |
| Treatment B (Part 1) | Active comparator | Tenofovir disoproxil fumarate 300 mg once daily for 5 days Receives: Drug: Tenofovir Disoproxil Fumarate |
| Treatment B (Part 2) | Active comparator | Raltegravir 400 mg twice daily for 5 days Receives: 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 Receives: 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 Receives: Drug: Narlaprevir; Drug: Ritonavir; Drug: Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of Narlaprevir
Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start24 Apr 2017
- Primary completion24 Jun 2017
- Study completion30 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- R-Pharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Almedis
- Responsible party
- Sponsor
- Investigators
- Mikhail Samsonov, Study director, R-Pharm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537404
- Sponsor's protocol ID
- CJ05013019
- Status last verified
- Aug 2018
- First submitted
- 15 May 2018
- Last updated
- 19 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs
- ClinicalTrials.gov ID
- NCT03537404
- Acronym / sponsor ID
- CJ05013019
- Conditions
- Healthy
- Keywords
- hepatitis C, chronic, pharmacokinetics, HIV, coinfection, concomitant therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- R-PharmIndustry (pharma, biotech, devices)
- Collaborators
- Almedis
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 24 Jun 2017 (actual)
- Study completion
- 30 Jun 2017 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Posted 19 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treatment A (Part 1/ Part 2) | Active comparator | Drug: Narlaprevir, Drug: RitonavirNarlaprevir 200 mg once daily with Ritonavir 100 mg once daily for 5 days |
| Treatment B (Part 1) | Active comparator | Drug: Tenofovir Disoproxil FumarateTenofovir disoproxil fumarate 300 mg once daily for 5 days |
| Treatment B (Part 2) | Active comparator | Drug: RaltegravirRaltegravir 400 mg twice daily for 5 days |
| Treatment C (Part 1) | Experimental | Drug: Narlaprevir, Drug: Ritonavir, Drug: Tenofovir Disoproxil FumarateNarlaprevir 200 mg once daily coadministered with ritonavir 100 mg once daily and Tenofovir disoproxil fumarate 300 mg once daily for 5 days |
| Treatment C (Part 2) | Experimental | Drug: Narlaprevir, Drug: Ritonavir, Drug: RaltegravirNarlaprevir 200 mg once daily coadministered with ritonavir 100 mg once daily and 400 mg raltegravir twice daily for 5 days |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NarlaprevirAlso: Arlansa100 mg, film-coated tablets, taken as 200 mg per os daily | Drug | Treatment A (Part 1/ Part 2), Treatment C (Part 1), Treatment C (Part 2) |
| RitonavirAlso: Norvir100 mg, film-coated tablets, taken as 100 mg per os daily | Drug | Treatment A (Part 1/ Part 2), Treatment C (Part 1), Treatment C (Part 2) |
| Tenofovir Disoproxil FumarateAlso: Tenofovir-TL, Viread300 mg, film-coated tablets, taken as 300 mg per os daily | Drug | Treatment B (Part 1), Treatment C (Part 1) |
| RaltegravirAlso: Isentress400 mg, film-coated tablets, taken as 400 mg per os daily | Drug | Treatment B (Part 2), Treatment C (Part 2) |
Primary outcome
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
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
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
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
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
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
4 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
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
Time frame: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikhail Samsonov study director
R-Pharm
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Narlaprevir, Ritonavir and Tenofovir Disoproxil Fumarate in people with Healthy, run by R-Pharm at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2019.