Pharmacokinetics and Pharmacodynamics of Sublingual BuprenorphinePhase 1PosaBupreNCT01367808
Effects of Posaconazole and Voriconazole on the Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine
A Phase 1 study testing vorikonazole and posakonazole in people with Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine, run by Turku University Hospital at 1 site in Finland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine
- What is being tested?
- vorikonazole and posakonazole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteFinland
- Study dates
- Feb 2011to Apr 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers
- Age 18-40
- Body weight within ±15% of the ideal weight for height
Who cannot join
- A previous history of intolerance to the study drugs or to related compounds and additives
- Concomitant drug therapy of any kind for at least 14 days prior to the study
- Existing or recent significant disease
- History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders
- History of asthma or any kind of drug allergy
- 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
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- A positive test result for urine toxicology
- A "yes" answer to any one of the Abuse Questions
- Pregnancy or nursing
- Donation of blood for 4 weeks prior and during the study
- Special diet or life style conditions which would compromise the conditions of the study or interpretation of the results
- Participation in any other studies involving investigational or marketed drug products concomitantly or within one month prior to the entry into this study
- Smoking for one month before the start of the study and during the whole study period
- Any history of coagulation abnormality, also in first degree relatives
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Posaconazole and Voriconazole on the Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine: A Three-phase Cross-over Study in Healthy Subjects
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.
Read more
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.
- Being tested
- Placebo, vorikonazole, posakonazole
- Keywords
- Buprenorphine, Vorikonazole, Posakonazole, Interactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
The subjects will be given placebo twice a day for 5 days prior to the study
vorikonazoleDrug
The subject will be given vorikonazole twice a day for 5 days prior to the study. The dose will be 400 mg twice a day on day one ans 200 mg twice a day on days 2-5.
posakonazoleDrug
The subjects will be given posaconazole 400 mg twice a day for 5 days prior to the study.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Vorikonazole | Active comparator | Not described Receives: Drug: vorikonazole |
| Posakonazole | Active comparator | Not described Receives: Drug: posakonazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of buprenorphine and its metabolites in plasma and urine
Measured: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 20 hours after administration of buprenorphine
Secondary outcomes (2)
Pharmacodynamic effects
The psychomotor effects on buprenorphine will be assessed with the measurement of pupil size, Maddox wing test and digit symbol substitution test
Measured: 1, 2,3, 4, 5, 6, 8, 10, 12, hours after administration of buprenorphine
Analgesia
The analgesic effect of buprenorphine will be evaluated using the cold pressor test. Briefly, the subject's hand is immersed into ice-cold water of + 4° 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. Cold pain threshold is defined as the latency from the immersion of the hand to the subject's first report of pain. Cold pain intensity is assessed at 30 s intervals following immersion of the hand in cold water for up to 60s . A verbal numerical rating scale of 0-100 will be used.
Measured: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of buprenorphine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startFeb 2011
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetics and Pharmacodynamics of Sublingual BuprenorphineStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Investigators
- Klaus T Olkkola, professor, Principal investigator, Turku University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367808
- Sponsor's protocol ID
- 55/180/2010
- Acronym
- PosaBupre
- Status last verified
- Dec 2010
- First submitted
- 30 May 2011
- Last updated
- 7 Jun 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Posaconazole and Voriconazole on the Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine: A Three-phase Cross-over Study in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01367808
- Acronym / sponsor ID
- PosaBupre / 55/180/2010
- Keywords
- Buprenorphine, Vorikonazole, Posakonazole, Interactions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Turku University HospitalOther government
- Study start
- Feb 2011
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 7 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Vorikonazole | Active comparator | Drug: vorikonazole |
| Posakonazole | Active comparator | Drug: posakonazole |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy volunteers
- Age 18-40
- Body weight within ±15% of the ideal weight for height
Key exclusion criteria (14 listed)
- A previous history of intolerance to the study drugs or to related compounds and additives
- Concomitant drug therapy of any kind for at least 14 days prior to the study
- Existing or recent significant disease
- History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders
- History of asthma or any kind of drug allergy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboThe subjects will be given placebo twice a day for 5 days prior to the study | Drug | Placebo |
| vorikonazoleThe subject will be given vorikonazole twice a day for 5 days prior to the study. The dose will be 400 mg twice a day on day one ans 200 mg twice a day on days 2-5. | Drug | Vorikonazole |
| posakonazoleThe subjects will be given posaconazole 400 mg twice a day for 5 days prior to the study. | Drug | Posakonazole |
Primary outcome
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
2 secondary outcomes
Pharmacodynamic effects
Time frame: 1, 2,3, 4, 5, 6, 8, 10, 12, hours after administration of buprenorphine
Analgesia
Time frame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of buprenorphine
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2011.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klaus T Olkkola, professor principal investigator
Turku University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing vorikonazole and posakonazole in people with Pharmacokinetics and Pharmacodynamics of Sublingual Buprenorphine, run by Turku University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2011.