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The Pharmacokinetics of Gefapixant (MK-7264) in Participants With Renal Insufficiency (MK-7264-026)

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ClinicalTrials.gov Identifier: NCT03108924
Recruitment Status : Completed
First Posted : April 11, 2017
Last Update Posted : September 20, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This trial aims to evaluate the plasma pharmacokinetics of gefapixant (MK-7264) administered to participants with varying degrees of renal insufficiency (RI) compared to healthy matched controls; and to investigate the extent of MK-7264 removal by hemodialysis in participants with end stage renal disease (ESRD), following administration of a single 50 mg dose of gefapixant.

Condition or disease Intervention/treatment Phase
Renal Insufficiency Drug: Gefapixant Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Dose Study to Investigate the Influence of Renal Insufficiency on the Pharmacokinetics of MK-7264
Actual Study Start Date : April 14, 2017
Actual Primary Completion Date : September 3, 2017
Actual Study Completion Date : September 13, 2017

Arm Intervention/treatment
Experimental: Moderate RI
Participants with moderate renal insufficiency (RI) are treated with a single 50 mg dose of gefapixant
Drug: Gefapixant
After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.
Other Name: MK-7264

Experimental: Severe RI
Participants with severe RI are treated with a single 50 mg dose of gefapixant
Drug: Gefapixant
After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.
Other Name: MK-7264

Healthy Matched Controls
Healthy, participants matched for age and body weight are treated with a single 50 mg dose of gefapixant
Drug: Gefapixant
After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.
Other Name: MK-7264

Experimental: ESRD Requiring HD
Participants with end stage renal disease (ESRD) requiring hemodialysis (HD), are treated in Period 1 with a single 50 mg dose of gefapixan immediately after the scheduled HD; followed in Period 2 with a single 50 mg dose of gefapixan two hours prior to HD. Between the Periods 1 and 2 MK-7264 dosings there will be a 7-day washout period with 3 dialysis sessions.
Drug: Gefapixant
After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.
Other Name: MK-7264




Primary Outcome Measures :
  1. Concentration-time curve up to infinity [ Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of plasma gefapixant in RI, healthy, matched, and ESRD participants

  2. Concentration-time curve up to last measurement [ Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]
    Area under the concentration-time curve from time 0 to the last measurement (AUC0-last) of plasma gefapixant in RI, healthy, matched, and ESRD participants

  3. Maximum concentration [ Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]
    Maximum concentration (Cmax) of plasma gefapixant in RI, healthy, matched, and ESRD participants

  4. Total Clearance [ Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose ]
    Apparent total clearance (CL/F) of plasma gefapixant in RI, healthy, matched, and ESRD participants

  5. Renal Clearance [ Time Frame: Spot collection at predose, 0-12 hours, 12-24 hours and 24-48 hours postdose ]
    Renal clearance (CLr) of urinal gefapixant in RI and healthy, matched participants

  6. Concentration-time curve from 0-4 hours HD (pre-dialysis) [ Time Frame: Period 2: 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours postdose ]
    Area under the concentration-time curve from time 0 to 4 hours during HD of pre-dialyzer line plasma gefapixant (AUCD) in participants with ESRD.

  7. Concentration-time curve from 2.5-6 hours HD (pre-dialysis) [ Time Frame: Period 2: 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours postdose ]
    Area under the concentration-time curve from time 2.5 to 6 hours during HD of pre-dialyzer line plasma gefapixant (AUC(2.5-6)Ca) in participants with ESRD.

  8. Concentration-time curve from 2.5-6 hours HD (post-dialysis) [ Time Frame: Period 2: 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours postdose ]
    Area under the concentration-time curve from time 2.5 to 6 hours during HD of post-dialyzer line plasma gefapixant (AUC(2.5-6)Cv) in participants with ESRD.


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: Up to Day 16 ]
    Number of participants with an Adverse Event (AE)

  2. Discontinuations [ Time Frame: Day 1 ]
    Number of participants who discontinued study treatment due to an AE



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Is a non-smoker or moderate smoker (≤ 20 cigarettes/day or the equivalent) who agrees to consume no more than 10 cigarettes or equivalent/day from the time of screening and throughout the period of sample collection.
  • Has a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m2,
  • Is judged to be in good health based on medical history, physical examination, vital signs, and laboratory safety tests. Has no clinically significant electrocardiogram (ECG) abnormality, as deemed by the Investigator.
  • Females are non-pregnant, and non-breast feeding. If female with reproductive potential, they must demonstrate they are not pregnant and agree to use (and/or have their partner use) two (2) acceptable methods of birth control beginning at screening, throughout the study and until 2 weeks after dosing of study drug.
  • Participants with ESRD requiring HD has been maintained on stable regimen of thrice-weekly HD for at least 3 months prior to first dosing.
  • Healthy participants, must be within ± 10 years of the mean age of participants with RI; and must be within ± 10 kg of the mean weight of participants with RI.

Exclusion Criteria:

  • Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit, or expected during the conduct of the study.
  • Has a history or presence of clinically significant medical or psychiatric condition or disease.
  • Has a history of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk by participating in the study.
  • Has a history or presence of alcoholism or drug abuse within the past 6 months prior to dosing.
  • Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds (including sulfonamides).
  • Has a history or presence of renal artery stenosis; or major risk factors for renal/urinary calculi.
  • Has rapidly fluctuating renal function as determined by historical measurements.
  • Female who is pregnant, or lactating.
  • Has positive results for urine or saliva drug and/or urine or breath alcohol at screening or check-in.
  • Is positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
  • Has positive macroscopic hematuria or crystalluria at screening or check-in.
  • Is unable to refrain from or anticipates using any medication or substance including prescription or over-the-counter, vitamin supplements, natural or herbal supplements.
  • Has been on a diet incompatible with the on-study diet, within the 28 days prior to dosing.
  • Has donated blood or had significant blood loss within 56 days prior to dosing.
  • Has donated plasma within 7 days prior to dosing.
  • Has taken gefapixant at any time prior to dosing on the current study.
  • Has participated in another clinical trial within 28 days prior to dosing based on the latest blood collection or dosing.

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): NCT03108924


Locations
United States, Florida
Clinical Pharmacology of Miami ( Site 0001)
Hialeah, Florida, United States, 33014
Orlando Clinical Research Center ( Site 0002)
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03108924     History of Changes
Other Study ID Numbers: 7264-026
First Posted: April 11, 2017    Key Record Dates
Last Update Posted: September 20, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases