E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is aimed to examine the possible interactions of sublingual and intravenous buprenorphine with rifampicin |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Twelve male or female adult non-smoking subjects aged 1840 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 (Michna et al. 2004) 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.
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E.4 | Principal exclusion criteria |
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) |
On day 7, 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18-20 hours after administration |
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E.5.2 | Secondary end point(s) |
The psychomotor effects of buprenorphine will be assessed with visual analogue scales (Bond and Lader 1974) and digit symbol substitution test (Stone 1984) at 12 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. The cold pain test has been shown to be sensitive to opioid analgesia, and it enables repeated assessments of cold pain threshold, tolerance, intensity and unpleasantness (Grach et al. 2004). Briefly, the hand contra lateral to the venous cannula for blood sampling is immersed into ice-cold water of + 4º C up to the wrist. The subject is told to keep his or her hand in the water and to report when the cold sensation becomes painful. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
On day 7 prior to the challenge dose of buprenorphine and after the venous blood samples at 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the challenge dose.
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |