HealthyPhase 4NCT01854489
Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of Sublingual and Intravenous Buprenorphine
A Phase 4 study testing Rifampicin and Buprenorphine in people with Healthy, run by Turku University Hospital at 1 site in Finland.
Trial summary
This study is aimed to examine the possible interactions of sublingual and intravenous buprenorphine with rifampicin. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Rifampicin and Buprenorphine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteFinland
- Study dates
- Apr 2013to Nov 2014
- Phase
- Phase 4
- 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
- non-smoking
- aged 18-40 years
- body weights 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.
- Subjects younger than 18 years and older than 40 years.
- 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.
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- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of Sublingual and Intravenous Buprenorphine: A Four-phase Cross-over Study in Healthy Subjects.
This study is aimed to examine the possible interactions of sublingual and intravenous buprenorphine with rifampicin.
Read the detailed 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.Buprenorphine is a semisynthetic partial µ-opioid receptor agonist. In low doses, it is used in the treatment of moderate acute and chronic pain whereas in high doses, it is used in the management of opioid withdrawal symptoms and opioid addiction. It has high affinity for the µ-opioid receptor and its analgesic efficacy is 20-40 times that of morphine. It acts as an antagonist at the myy-opioid receptor and as an agonist at the myy-opioid receptor and opioid-like receptor (ORL-1).
Buprenorphine undergoes extensive first-pass metabolism and has low oral bioavailability of 15 %. Bioavailability following sublingual administration of buprenorphine is higher, 50-60 %. After high sublingual doses of buprenorphine (8-24 mg), peak plasma concentrations are reached in 1 hour and after low sublingual doses (0.4 mg) they are reached in approximately 3 h. Approximately two-thirds of a buprenorphine dose is excreted unchanged, and the rest is metabolized in the liver and intestinal wall. N-dealkylation of buprenorphine mainly via CYP3A but also CYP2C8 yields norbuprenorphine, and glucuronidation yields buprenorphine-3-glucuronide. Norbuprenorphine is excreted in the urine after subsequent conjugation. 80-90 % of buprenorphine is excreted by the biliary system and enterohepatic circulation.Although few interaction studies of high-dose buprenorphine and antiretrovirals have been conducted, the effect of CYP3A inducers on the pharmacokinetics of low-dose buprenorphine is unknown. Because the use of buprenorphine in pain management is increasing after the introduction of transdermal buprenorphin patches to the market, it is clinically relevant to study and quantify possible interactions of buprenorphine with inducers of its CYP3A-mediated metabolism such as rifampicin.
- Conditions
- Healthy
- Being tested
- Placebo, Rifampicin, Buprenorphine
- Keywords
- Buprenorphine, Rifampicin, Interactions, Pharmakokinetics, Pharmakodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
The volunteers will be given Oral placebo at 20.00 for 7 days [Phase 1 ]
RifampicinDrug
The volunteers will be given oral rifampicin (Rimapen, Orion, Finland) 600 mg as a single daily dose at 20.00 for 7 days
BuprenorphineDrug
Also called Temgesic 0,2 mg resoriblet, Temgesic 0,3 mg/ml
The volunteers will be given single dose of 0,4 mg intra venous buprenorphine or 0,6 mg sublingual buprenorphine on day 5.
| Study group | Role | What they receive |
|---|---|---|
| Rifampicin | Active comparator | The volunteers will be given oral rifampicin (Rimapen, Orion, Finland) 600 mg as a single daily dose at 20.00 for 7 days Receives: Drug: Rifampicin |
| Placebo | Placebo comparator | The volunteers will be given oral placebo at 20.00 for 7 days Receives: Drug: Placebo |
| Buprenorphine | Active comparator | The volunteers will be given single dose of 0,4 mg intra venous buprenorphine or 0,6 mg sublingual buprenorphine on day 5. Receives: Drug: Buprenorphine |
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 concebtration of buprenorphine
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 bubrenorphine will be assessed with the measurement of pupil size, Maddox wing test and symbol substitution test.
Measured: 1, 2,3, 4, 5, 6, 8, 10, 12, 20 hours after administration of buprenorphine
Analgesia
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
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 posted15 May 2013 (estimated)
- Study startApr 2013
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Mari Fihlman, Turku University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01854489
- Sponsor's protocol ID
- Rifabupre
- Status last verified
- Nov 2014
- First submitted
- 27 Apr 2013
- Last updated
- 20 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of Sublingual and Intravenous Buprenorphine: A Four-phase Cross-over Study in Healthy Subjects.
- ClinicalTrials.gov ID
- NCT01854489
- Acronym / sponsor ID
- Rifabupre
- Conditions
- Healthy
- Keywords
- Buprenorphine, Rifampicin, Interactions, Pharmakokinetics, Pharmakodynamics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Study start
- Apr 2013
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 15 May 2013 (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.
This study is aimed to examine the possible interactions of sublingual and intravenous buprenorphine with rifampicin.
Detailed 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.Buprenorphine is a semisynthetic partial µ-opioid receptor agonist. In low doses, it is used in the treatment of moderate acute and chronic pain whereas in high doses, it is used in the management of opioid withdrawal symptoms and opioid addiction. It has high affinity for the µ-opioid receptor and its analgesic efficacy is 20-40 times that of morphine. It acts as an antagonist at the myy-opioid receptor and as an agonist at the myy-opioid receptor and opioid-like receptor (ORL-1).
Buprenorphine undergoes extensive first-pass metabolism and has low oral bioavailability of 15 %. Bioavailability following sublingual administration of buprenorphine is higher, 50-60 %. After high sublingual doses of buprenorphine (8-24 mg), peak plasma concentrations are reached in 1 hour and after low sublingual doses (0.4 mg) they are reached in approximately 3 h. Approximately two-thirds of a buprenorphine dose is excreted unchanged, and the rest is metabolized in the liver and intestinal wall. N-dealkylation of buprenorphine mainly via CYP3A but also CYP2C8 yields norbuprenorphine, and glucuronidation yields buprenorphine-3-glucuronide. Norbuprenorphine is excreted in the urine after subsequent conjugation. 80-90 % of buprenorphine is excreted by the biliary system and enterohepatic circulation.Although few interaction studies of high-dose buprenorphine and antiretrovirals have been conducted, the effect of CYP3A inducers on the pharmacokinetics of low-dose buprenorphine is unknown. Because the use of buprenorphine in pain management is increasing after the introduction of transdermal buprenorphin patches to the market, it is clinically relevant to study and quantify possible interactions of buprenorphine with inducers of its CYP3A-mediated metabolism such as rifampicin.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rifampicin | Active comparator | Drug: RifampicinThe volunteers will be given oral rifampicin (Rimapen, Orion, Finland) 600 mg as a single daily dose at 20.00 for 7 days |
| Placebo | Placebo comparator | Drug: PlaceboThe volunteers will be given oral placebo at 20.00 for 7 days |
| Buprenorphine | Active comparator | Drug: BuprenorphineThe volunteers will be given single dose of 0,4 mg intra venous buprenorphine or 0,6 mg sublingual buprenorphine on day 5. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- non-smoking
- aged 18-40 years
- body weights 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.
- Subjects younger than 18 years and older than 40 years.
- Existing or recent significant disease.
- History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders.
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 volunteers will be given Oral placebo at 20.00 for 7 days [Phase 1 ] | Drug | Placebo |
| RifampicinThe volunteers will be given oral rifampicin (Rimapen, Orion, Finland) 600 mg as a single daily dose at 20.00 for 7 days | Drug | Rifampicin |
| BuprenorphineAlso: Temgesic 0,2 mg resoriblet, Temgesic 0,3 mg/mlThe volunteers will be given single dose of 0,4 mg intra venous buprenorphine or 0,6 mg sublingual buprenorphine on day 5. | Drug | Buprenorphine |
Primary outcome
Concentration of buprenorphine and its metabolites in plasma and urine concebtration of buprenorphine
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, 20 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 20 Nov 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifampicin and Buprenorphine in people with Healthy, 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 20 Nov 2014. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 concebtration of buprenorphine (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 20 Nov 2014.