- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02715700
Effects of Doravirine (MK-1439) on Methadone Pharmacokinetics in Methadone-Maintained Participants (MK-1439-045)
12 juni 2019 uppdaterad av: Merck Sharp & Dohme LLC
A Multiple-Dose Clinical Trial to Study the Effect of MK-1439 (Doravirine) on Methadone Pharmacokinetics
This study will evaluate the effects of multiple doses of doravirine (MK-1439) on the pharmacokinetics of methadone in participants requiring methadone maintenance therapy.
The primary hypothesis is that area under the plasma concentration-time curve to 24 hours postdose (AUC0-24) of (R)-methadone is similar when a maintenance regimen of methadone is administered with or without multiple daily doses of doravirine.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Faktisk)
14
Fas
- Fas 1
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 65 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Ja
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- If female with reproductive potential: must demonstrate a serum β-human chorionic gonadotropin (β -hCG) level consistent with the nongravid state and agree to use (and/or have their partner use) two acceptable methods of birth control throughout the trial and until 2 weeks after the last dose of trial drug.
- If postmenopausal female: must be without menses for at least 1 year.
- If surgically sterile female: must have a status of post hysterectomy, oophorectomy or tubal ligation.
- Body Mass Index (BMI) of 18-35 kg/m^2 (inclusive).
- Able to comply with the smoking restrictions, including <=10 cigarettes per day while in the Clinical Research Unit, and no smoking from 2 hours predose to 2 hours postdose on Days 1 and 6.
- Reliably participating in a methadone maintenance program for at least two months prior to Day 1. Required to be on a documented stable dose of methadone for at least 14 days prior to Day 1.
- Agree not to change current maintenance methadone dose of 20-200 mg once daily (unless for safety reasons) from screening until the end of the study. Must agree to observation and documentation of daily methadone dose administration during the period of the study during which they are domiciled.
Exclusion Criteria:
- Mentally or legally incapacitated, have significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or have a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the trial at the discretion of the investigator.
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the trial at the discretion of the investigator.
- History of cancer (malignancy) - exceptions apply.
- History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
- Positive for Human Immunodeficiency Virus (HIV).
- Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
- Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit.
- Nursing mother.
- Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to the first dose of the 14 day methadone maintenance phase prior to Day 1, throughout the trial, until the post-trial visit - exceptions apply.
- Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day - exceptions apply.
- Consumes excessive amounts of caffeine, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
- Has a positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines (exceptions apply), or opiates/opioids (apart from methadone as assigned maintenance therapy) on Day 1 that cannot be explained by concomitant medications, unless at the discretion of the principal investigator and the sponsor. Must have a negative Urine Drug Screen prior to randomization, with the exception of tetrahydrocannabinol (THC) and prescription benzodiazepines.
- Clinical Opiate Withdrawal Scale (COWS) score of >=5 prior to randomization.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Maintenance Methadone and MK-1439
Participants maintained on a stable methadone regimen (20 to 200 mg once daily) for ≥14 days prior to Day 1 will continue to receive methadone maintenance once per day on Days 1 to 7. From Day 2 to 6, participants will also receive doravirine 100 mg once daily.
|
Methadone 20 to 200 mg (10 mg/mL if oral solution concentrate) oral tablet once per day.
Doravirine 100 mg oral tablet once per day.
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Area Under the Concentration-Time Curve From Zero to 24 Hours After Dosing (AUC0-24) of R-Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The AUC0-24 of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by liquid chromatographic-tandem mass spectrometric (LC-MS/MS) detection.
The lower limit of quantification (LLoQ) was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
Plasma Concentration at 24 Hours After Dosing (C24) of R-Methadone
Tidsram: 24 hours postdose on Day 1 and Day 6
|
The C24 of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
24 hours postdose on Day 1 and Day 6
|
Maximum Plasma Concentration (Cmax) of R-Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The Cmax of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
Time to Maximum Plasma Concentration (Tmax) of R-Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The Tmax of the R- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
AUC0-24 of S-Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The AUC0-24 of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
C24 of S-Methadone
Tidsram: 24 hours postdose on Day 1 and Day 6
|
The C24 of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
24 hours postdose on Day 1 and Day 6
|
Cmax of S-Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The Cmax of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
Tmax of S-Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The Tmax of the S- methadone enantiomer was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
AUC0-24 of Total Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The AUC0-24 of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
C24 of Total Methadone
Tidsram: 24 hours postdose on Day 1 and Day 6
|
The C24 of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
24 hours postdose on Day 1 and Day 6
|
Cmax of Total Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The Cmax of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
Tmax of Total Methadone
Tidsram: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
The Tmax of total methadone was determined on Day 1 (methadone alone) and on Day 6 (methadone + doravirine).
Plasma samples collected for methadone assay were analyzed for R- and S-methadone concentrations by Pharma Medica Research Inc. (Ontario, Canada).
The analytical method used liquid-liquid extraction for analyte isolation followed by LC-MS/MS detection.
The LLoQ was 0.0250 ng/mL for each enantiomer.
The analytical range was 0.0250 - 15.0 ng/mL.
|
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose on Day 1 and Day 6
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
28 september 2015
Primärt slutförande (Faktisk)
13 juni 2016
Avslutad studie (Faktisk)
15 augusti 2016
Studieregistreringsdatum
Först inskickad
17 mars 2016
Först inskickad som uppfyllde QC-kriterierna
21 mars 2016
Första postat (Uppskatta)
22 mars 2016
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
25 juni 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
12 juni 2019
Senast verifierad
1 juni 2019
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- RNA-virusinfektioner
- Virussjukdomar
- Infektioner
- Blodburna infektioner
- Smittsamma sjukdomar
- Sexuellt överförbara sjukdomar, virala
- Sexuellt överförbara sjukdomar
- Lentivirusinfektioner
- Retroviridae-infektioner
- Immunologiska bristsyndrom
- Immunsystemets sjukdomar
- Långsamma virussjukdomar
- HIV-infektioner
- Förvärvat immunbristsyndrom
- Läkemedels fysiologiska effekter
- Depressiva medel i centrala nervsystemet
- Agenter från det perifera nervsystemet
- Analgetika
- Sensoriska systemagenter
- Analgetika, Opioid
- Narkotika
- Andningsorgan
- Hostdämpande medel
- Metadon
Andra studie-ID-nummer
- 1439-045
- MK-1439-045 (Annan identifierare: Merck Protocol Number)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Infektion med humant immunbristvirus (HIV).
-
Institut PasteurRekrytering
-
Janssen-Cilag International NVAvslutadInfektioner av humant immunbristvirus (HIV). | Aids-virus (Acquired Immunodeficiency Syndrome).Frankrike, Storbritannien, Belgien, Tyskland, Spanien, Schweiz, Danmark, Israel, Österrike, Polen, Ungern, Sverige, Irland
-
University Hospital, GenevaAvslutadHPV - Anogenital Human Papilloma Virus Infection
-
Stanford UniversityAnmälan via inbjudanHPV - Anogenital Human Papilloma Virus InfectionFörenta staterna
-
Centre Hospitalier Universitaire Saint PierreAktiv, inte rekryterandeHIV-infektioner | HPV - Anogenital Human Papilloma Virus InfectionBelgien
-
Ann & Robert H Lurie Children's Hospital of ChicagoNorthwestern University; Florida State UniversityIndragenHepatit A | Hjärnhinneinflammation | HPV - Anogenital Human Papilloma Virus Infection
-
Hospital Universitari de BellvitgeInstitut d'Investigació Biomèdica de BellvitgeOkändHiv | Anal cancer | HPV - Anogenital Human Papilloma Virus Infection | HSIL, höggradiga skvamösa intraepitelial lesionerSpanien
-
Bayside HealthGilead SciencesOkändHIV-infektioner | Hepatit B-virusAustralien
-
Rockefeller UniversityAvslutadHIV-infektioner | Hepatit C-virusFörenta staterna
-
ANRS, Emerging Infectious DiseasesUniversity Hospital, Geneva; University of Bordeaux; International Agency... och andra samarbetspartnersRekryteringHIV-infektioner | HPV - Anogenital Human Papilloma Virus InfectionBurkina Faso, Kambodja, Elfenbenskusten