Renal ImpairmentPhase 1NCT02641067

A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)

A Phase 1 study testing Doravirine in people with Renal Impairment, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study will evaluate the effect of severe renal impairment on the pharmacokinetics of doravirine. Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Renal Impairment
What is being tested?: Doravirine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: No sites listed yet
Study dates: 26 Jan 2016to 25 May 2016
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 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

is a non-smoker or moderate smoker
has a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m^2
other than renal impairment, participant is judged to be in good health based on medical history, physical examination, vital signs, and laboratory safety tests
female informed of the risks of pregnancy, agree not to become pregnant while participating in this study. Female of childbearing potential must either be sexually inactive for 14 days prior to dosing and throughout the study, or uses one acceptable birth control method
female of non-childbearing potential must have undergone sterilization procedures at least 6 months prior to dosing.
Participants with severe renal impairment only: has baseline estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2

Who cannot join

is mentally or legally incapacitated or has significant emotional problems
has a history or presence of clinically significant medical or psychiatric condition or disease
has history or presence of alcoholism or drug abuse within the past 2 years
has history or presence of hypersensitivity or idiosyncratic reaction to the study drug, any inactive ingredients, or related compounds
has history or presence of renal artery stenosis
has had a renal transplant or nephrectomy

Show all 16Show fewer

has rapidly fluctuating renal function as determined by historical measurements
female is pregnant or lactating
has positive results for the urine or saliva drug and urine or breath alcohol screen at screening or check-in
has positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
is unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to dosing and throughout the study. Certain medications including those to treat kidney disease will be permitted. Other medications may be permitted following consultation with the Sponsor Clinical Monitor.
is unable to refrain from or anticipates the use of inducers of cytochrome P450 3A (CYP3A) or permeability glycoprotein (P-gp) transporters for at least 28 days prior to dosing and throughout the study.
has been on a diet incompatible with the on-study diet, within 28 days prior to dosing, and throughout the study
has donated blood or had significant blood loss within 56 days prior to dosing
has donated plasma within 7 days prior to dosing
has participated in another clinical trial within 28 days prior to dosing

About this study

Official title: An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-1439 (Doravirine) in Subjects With Severe Renal Impairment

This study will evaluate the effect of severe renal impairment on the pharmacokinetics of doravirine.

Conditions: Renal Impairment
Being tested: Doravirine
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DoravirineDrug
Also called MK-1439, PIFELTRO
Following an overnight fast, a single coated tablet of 100 mg doravirine will be administered orally

Study groups in NCT02641067
Study group	Role	What they receive
Severe Renal Impairment	Experimental	Participants with severe renal impairment receive a single oral dose of 100 mg doravirine Receives: Drug: Doravirine
Healthy Matched Control	Experimental	Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine Receives: Drug: Doravirine

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Plasma Concentration of Doravirine at 24 Hours Postdose (C24)
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: 24 hours postdose
Maximum Observed Plasma Concentration (Cmax) of Doravirine
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Apparent Terminal Half-life (t1/2) of Plasma Doravirine
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Jan 201625 May 2016

First posted29 Dec 2015 (estimated)
Study start26 Jan 2016
Primary completion14 May 2016
Study completion25 May 2016

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02641067
Sponsor's protocol ID: 1439-051
Other IDs: MK-1439-051
Status last verified: Sep 2018
First submitted: 23 Dec 2015
Last updated: 8 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Ankrom W, Yee KL, Sanchez RI, Adedoyin A, Fan L, Marbury T, Preston RA, Iwamoto M, Khalilieh SG. Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00326-18. doi: 10.1128/AAC.00326-18. Print 2018 Aug.
PubMed 29891610

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 2
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Not yet recruiting
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All Renal Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-1439 (Doravirine) in Subjects With Severe Renal Impairment
ClinicalTrials.gov ID: NCT02641067
Acronym / sponsor ID: 1439-051
Conditions: Renal Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 26 Jan 2016 (actual)
Primary completion: 14 May 2016 (actual)
Study completion: 25 May 2016 (actual)
First posted: 29 Dec 2015 (estimated)
Results: Posted 8 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will evaluate the effect of severe renal impairment on the pharmacokinetics of doravirine.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Severe Renal Impairment	Experimental	Drug: DoravirineParticipants with severe renal impairment receive a single oral dose of 100 mg doravirine
Healthy Matched Control	Experimental	Drug: DoravirineHealthy participants matched for age and weight receive a single oral dose of 100 mg doravirine

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

is a non-smoker or moderate smoker
has a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m^2
other than renal impairment, participant is judged to be in good health based on medical history, physical examination, vital signs, and laboratory safety tests
female informed of the risks of pregnancy, agree not to become pregnant while participating in this study. Female of childbearing potential must either be sexually inactive for 14 days prior to dosing and throughout the study, or uses one acceptable birth control method
female of non-childbearing potential must have undergone sterilization procedures at least 6 months prior to dosing.

Key exclusion criteria (16 listed)

is mentally or legally incapacitated or has significant emotional problems
has a history or presence of clinically significant medical or psychiatric condition or disease
has history or presence of alcoholism or drug abuse within the past 2 years
has history or presence of hypersensitivity or idiosyncratic reaction to the study drug, any inactive ingredients, or related compounds
has history or presence of renal artery stenosis

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
DoravirineAlso: MK-1439, PIFELTROFollowing an overnight fast, a single coated tablet of 100 mg doravirine will be administered orally	Drug	Healthy Matched Control, Severe Renal Impairment

Primary outcome

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Plasma Concentration of Doravirine at 24 Hours Postdose (C24)
Time frame: 24 hours postdose
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Maximum Observed Plasma Concentration (Cmax) of Doravirine
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Apparent Terminal Half-life (t1/2) of Plasma Doravirine
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.

Results and safety

Results posted to the registry on 8 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Severe Renal Impairment	8	8
Healthy Matched Controls	8	8

Primary outcome: Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment. Geometric mean (95% Confidence Interval). Unit: μM•hr

Measure	Severe Renal Impairment n = 8	Healthy Matched Controls n = 8
Value	64.5 (47.4 to 87.8)	45.1 (33.2 to 61.4)

Severe Renal Impairment vs Healthy Matched Controls: Geometric mean ratio: 1.43 (90% CI 1.00 to 2.04)

Population analysed: All participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Primary outcome: Plasma Concentration of Doravirine at 24 Hours Postdose (C24)

Time frame: 24 hours postdose. Geometric mean (95% Confidence Interval). Unit: nM

Measure	Severe Renal Impairment n = 8	Healthy Matched Controls n = 8
Value	943 (710 to 1250)	684 (515 to 908)

Severe Renal Impairment vs Healthy Matched Controls: Geometric mean ratio: 1.38 (90% CI 0.99 to 1.92)

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Doravirine

Measure	Severe Renal Impairment n = 8	Healthy Matched Controls n = 8
Value	1580 (1210 to 2080)	1900 (1450 to 2500)

Severe Renal Impairment vs Healthy Matched Controls: Geometric mean ratio: 0.83 (90% CI 0.61 to 1.15)

Primary outcome: Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)

Measure	Severe Renal Impairment n = 8	Healthy Matched Controls n = 8
Value	60.5 (56.3)	41.0 (29.9)

Adverse events

Time frame: Up to 14 days after drug administration. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Severe Renal Impairment	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Healthy Matched Control	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29891610Ankrom W, Yee KL, Sanchez RI, Adedoyin A, Fan L, Marbury T, Preston RA, Iwamoto M, Khalilieh SG. Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00326-18. doi: 10.1128/AAC.00326-18. Print 2018 Aug.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Renal Impairment

Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant

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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Doravirine in people with Renal Impairment, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. 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 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

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 8 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?

Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine (time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 12, 24, 48, 72 hours post-dose for all participants; and 96 hours post-dose for participants with severe renal impairment). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02641067, which also lists 1 linked publication.

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 8 Feb 2019.