Back to resultsA Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)
Primary Purpose
Renal Impairment
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Doravirine
Sponsored by
About this trial
This is an interventional treatment trial for Renal Impairment
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Severe Renal Impairment
Healthy Matched Control
Arm Description
Participants with severe renal impairment receive a single oral dose of 100 mg doravirine
Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine
Outcomes
Primary Outcome Measures
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.
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.
Maximum Observed Plasma Concentration (Cmax) of Doravirine
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)
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
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
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)
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)
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Secondary Outcome Measures
Full Information
NCT ID
NCT02641067
First Posted
December 23, 2015
Last Updated
September 26, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02641067
Brief Title
A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)
Official Title
An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-1439 (Doravirine) in Subjects With Severe Renal Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
January 26, 2016 (Actual)
Primary Completion Date
May 14, 2016 (Actual)
Study Completion Date
May 25, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the effect of severe renal impairment on the pharmacokinetics of doravirine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Severe Renal Impairment
Arm Type
Experimental
Arm Description
Participants with severe renal impairment receive a single oral dose of 100 mg doravirine
Arm Title
Healthy Matched Control
Arm Type
Experimental
Arm Description
Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine
Intervention Type
Drug
Intervention Name(s)
Doravirine
Other Intervention Name(s)
MK-1439, PIFELTRO
Intervention Description
Following an overnight fast, a single coated tablet of 100 mg doravirine will be administered orally
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞) of Doravirine
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
Title
Plasma Concentration of Doravirine at 24 Hours Postdose (C24)
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
Time Frame
24 hours postdose
Title
Maximum Observed Plasma Concentration (Cmax) of Doravirine
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
Title
Area Under the Plasma Concentration Versus Time Curve From 0 Hours to the Time of Last Quantifiable Sample of Doravirine (AUC 0-last)
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
Title
Time to Maximum Observed Plasma Concentration (Tmax) of Doravirine
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
Title
Apparent Terminal Half-life (t1/2) of Plasma Doravirine
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
Title
Apparent Clearance of Plasma Doravirine After Extravascular Administration (CL/F)
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
Title
Apparent Volume of Distribution of Plasma Doravirine During the Terminal Phase (Vz/F)
Description
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
29891610
Citation
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.
Results Reference
derived
Learn more about this trial
A Study Evaluating the Pharmacokinetics of Doravirine (MK-1439) in Participants With Severe Renal Impairment (MK-1439-051)
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