NCT01367808: PosaBupre

Effects of Posaconazole and Voriconazole on the Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine: A Three-phase Cross-over Study in Healthy Subjects

Completed Phase 1 Last updated 6 June 2011

What this trial tests

Phase 1 trial testing Placebo in Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine in 12 participants. Completed in 1 April 2011.

Timeline

1 February 2011

Primary endpoint
1 April 2011

1 April 2011

Quick facts

Lead sponsor	Turku University Hospital
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	12
Start date	1 February 2011
Primary completion	1 April 2011
Estimated completion	1 April 2011
Sites	1 location across Finland

Drugs / interventions tested

• Placebo
• vorikonazole — full drug profile →
• posakonazole — full drug profile →

Conditions studied

• Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine — all drugs for Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine →

Sponsor

Turku University Hospital

Who can join

Adults 18 to 40, any sex, with Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Concentration of buprenorphine and its metabolites in plasma and urine
  Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 20 hours after administration of buprenorphine

Sponsor's own description

Variability in drug response can be due to either pharmacokinetic or pharmacodynamic factors. The reasons why people differ in pharmacokinetics or pharmacodynamics are manifold and include, e.g., genetic factors, diseases, age and concomitantly administered drugs. Oxidation reactions are dominant in the metabolism of drugs and cytochrome P-450 enzymes (CYP) have been recognized as chief contributors. We have previously shown that drug interactions mediated by the inhibition of CYP enzymes may be of major clinical significance.

This study is aimed to examine the possible interactions of low-dose sublingual buprenorphine with posaconazole and voriconazole.

The study will be conducted using a randomized, balanced cross-over design in three phases.

Twelve male or female adult non-smoking subjects aged 18-40 years with body weights within ±15% of the ideal weight for height will be recruited for the study. The subjects will be submitted to physical examination, determination of previous or present chronic diseases, and comprehensive laboratory testing to ascertain that they are in good health. The subjects will fill in a modified Finnish version of the Abuse Questions to assess their vulnerability for opioid abuse. Laboratory screening will include CBC (including hemoglobin, hematocrit, differential WBC, platelet count), SGOT, SGPT, alkaline phosphatase, BUN and creatinine, and for women a pregnancy test. Urine will be screened for glucose, proteins and drugs with addiction potential. Blood pressure in sitting position must be within normal limits. Base line ECG must be normal.

The subjects will be given in a randomized, cross-over, balanced manner at intervals of four weeks either placebo, vorikonazole or posakonazole. On day 5, the challenge dose of 0.4 or 0.6 mg of sublingual buprenorphine (Temgesic, Schering-Plough) will be administered at 11.00, i.e. 1 h after the last dose of placebo, voriconazole or posaconazole. The dose is 0.6 mg after placebo and 0.4 mg after posaconazole and voriconazole. If necessary, naloxone (Naloxone B. Braun, Braun) will be given in sufficient doses to counteract the severe adverse effects of buprenorphine. For nausea and vomiting, intravenous tropisetron will used, if needed.

On day 4, a forearm vein will be cannulated with a plastic cannula for blood sampling. Timed venous blood samples will be drawn before the administration of buprenorphine and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18-20 hours after administration. Another venous cannula will be inserted to the opposite forearm for the intravenous administration of naloxone. Urine will be collected for 18-20 hours.

The psychomotor effects of buprenorphine will be assessed with visual analog scales (Bond and Lader 1974) and digit symbol substitution test (Stone 1984) at 1-2 hour intervals up to 12 hours after buprenorphine administration. Visual analogue scales will be used for the following items: alert / drowsy, good / poor performance, no / strong drug effect, unpleasant /pleasant feeling, no / extreme nausea. For each pharmacodynamic variable, the area under the response-time curve will be determined by trapezoidal rule for 12 hours.

The analgesic effect of buprenorphine will be evaluated using the cold pressor test.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.