| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
- healty volunteer subjects
- The study is aimed to examine the possible interactions of low-dose sublingual buprenorphine with posaconazole and voriconazole. |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| This study is aimed to examine the possible interactions of low-dose sublingual buprenorphine with posaconazole and voriconazole. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Twelve male or female adult non-smoking subjects in good health aged 18-40 years with body weights within ±15% of the ideal weight for height will be recruited for the study. 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.
Subjects should not have taken any drugs or natural products, excluding alcohol, for at least 14 days prior to the study and no drugs known to cause enzyme induction or inhibition or grapefruit juice for a period of 30 days prior to the study. For women of childbearing age, safe nonhormonal contraception must be ensured. Subjects must give written informed consent.
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| E.4 | Principal exclusion criteria |
Criteria for exclusion
1. A previous history of intolerance to the study drugs or to related compounds and additives.
2.Concomitant drug therapy of any kind for at least 14 days prior to the study.
3.Subjects younger than 18 years and older than 40 years.
4.Existing or recent significant disease.
5.History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders.
6.History of asthma or any kind of drug allergy.
7.Previous or present alcoholism, drug abuse, psychological or other emotional problems that are likely to invalidate informed consent, or limit the ability of the subject to comply with the protocol requirements.
8.A positive test result for urine toxicology.
9.A “yes” answer to any one of the Abuse Questions.
10.Pregnancy or nursing.
11.Donation of blood for 4 weeks prior and during the study.
12.Special diet or life style conditions which would compromise the conditions of the study or interpretation of the results.
13.Participation in any other studies involving investigational or marketed drug products concomitantly or within one month prior to the entry into this study.
14.Smoking for one month before the start of the study and during the whole study period.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Pharmacokinetic and pharmacodynamic measurements
Pharmacokinetics: 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. Urine will be collected for 18-20 hours.
Buprenorphine, norbuprenorphine, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide concentrations will be analyzed with chromatographical methods. The urinary excretion of buprenorphine and its metabolites will be measured. For the control of compliance, plasma posaconazole and voriconazole concentrations will be measured before the administration of buprenorphine. The plasma pharmacokinetics of buprenorphine and its metabolites will be characterized by area under the drug plasma concentration-time curve (AUC0-∞), calculated using the trapezoidal rule. Elimination half-lives (T½), peak concentrations (Cmax) and concentration peak times (Tmax) will be calculated.
Pharmacodynamics: The psychomotor effects of buprenorphine will be assessed with visual analog scales and digit symbol substitution test 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.
Possible adverse effects: All volunteered and observed adverse effects will be recorded together with the time at which the effect was noted, its severity, duration and treatment.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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