PainPhase 1NCT03312777
Omnitram Pharmacokinetic and Analgesic Study Following CY2D6 Inhibition With Paroxetine In Healthy Volunteers
A Phase 1 study testing Omnitram and Tramadol in people with Pain, run by Syntrix Biosystems, Inc. at 1 site in United States.
Trial summary
This study evaluates the analgesic effect of Omnitram and tramadol during concurrent administration of paroxetine. Paroxetine administration is expected to diminish the analgesic effect of tramadol, but not Omnitram. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain
- What is being tested?
- Omnitram and Tramadol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2017to 22 Dec 2017
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males and females with normal vital signs: systolic blood pressure > 90 mm Hg and < 140 mm Hg; diastolic blood pressure > 45 mm Hg and < 90 mm Hg; pulse 40 to 100 beats per minute; respiratory rate 10 to 20 breathes per minute.
- Between the ages of 18 and 50 years of age.
- Able and willing to give informed consent
- Able to comply with all study procedures.
- If female, must not be of childbearing potential or must agree to use one or more of the following forms of contraception during screening and for 30 days following study drug administration: hormonal (e.g., oral, transdermal, intravaginal, implant or injection); double barrier (i.e., condom, diaphragm with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); abstinence; or bilateral tubal ligation.
- Have adequate hematologic function as evidenced by the following screening results:
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- WBC >3,500/mm3 and < 12,000/mm3 Platelet Count > 150,000/mm3 and < 540,000/mm3 Hemoglobin > 12.0 gm/dL and < 20.5 gm/dL
- Have adequate liver function as evidenced by the following screening results:
- AST (SGOT) ≤ 60 IU/L ALT (SGPT) men ≤ 83 IU/L women < 60 IU/L Alkaline Phosphatase ≤ 200 IU/L Total Bilirubin ≤ 1.2 mg/dL PT and PTT < 1.2 ULN
- Electrocardiogram (ECG) without clinically significant findings as determined by the PI.
- Have adequate renal function as evidenced by the following screening result:
- Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula >60 ml/min.
- Urinalysis demonstrating < +1 glucose, +1 ketones, and +1 protein.
- Negative pregnancy test within 1 week of study day 1 (women of childbearing potential only).
- Negative urine test for substances of abuse, including opiates, per CRU standards.
- Negative serology tests for HIV, hepatitis B surface antigen, and hepatitis C virus antibody.
- Body Mass Index (BMI) 18.0 to 32 kg/m.
- Cold pressor screening results as follows: 1) pain tolerance of > 20 seconds and <120 seconds.
- Cytochrome P450 2D6 (CYP2D6) genotype by Genelex consistent with intermediate metabolizer phenotype or normal metabolizer phenotype.
Who cannot join
- Oral temperature > 38°C or history of current illness.
- History of seizures, epilepsy, or recognized increase risk of seizure (e.g., head trauma, metabolic disorders, alcohol or drug withdrawal).
- History of cirrhosis or laboratory evidence of liver disease.
- Use of alcohol within 24 hours of day -1 until the end of the study; and grapefruit, grapefruit-related citrus fruits (e.g., Seville oranges, pomelos), or grapefruit juice or grapefruit-related juices, or other medication, within 7 days of study drug administration and until the end of the study.
- History of previous anaphylaxis, severe allergic reaction to paroxetine, tramadol, codeine, or other opioid drugs.
- Use of MAO Inhibitors (including linezolid), Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and prescription or over-the counter (OTC) medications known to induce or inhibit drug metabolism, including CYP2D6, and other drugs that may affect the serotonergic neurotransmitter systems including, but not limited to, triptans, dextromethorphan, tricyclic antidepressants, bupropion, lithium, tramadol, dietary supplements such as tryptophan and St. John's Wort, and antipsychotics or other dopamine antagonists. These restrictions are to be maintained from 14 days before study day -1, until the subject completes the study.
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- Any other unstable acute or chronic disease that could interfere with the evaluation of the safety of the study drug as determined by the principal Investigator in dialogue with the Sponsor Medical Monitor.
- Currently pregnant or breast feeding.
- Unlikely to comply with the study protocol.
- Known or suspected alcohol or drug abuse within the past 6 months.
- Received another investigational agent within 4 weeks of Day 1, or receiving any other investigational agent during this study.
- Any concurrent disease or condition that in the opinion of the investigator impairs the subject's ability to complete the trial. Psychological, familial, sociological, geographical or medical conditions which, in the Investigator's opinion, could compromise compliance with the objectives and procedures of this protocol, or obscure interpretation of the trial data.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1b, Double-Blind, Randomized, Placebo-Controlled, Three Segment Cross-Over Study Investigating Oral Steady-State Pharmacokinetics And Hypoalgesic Effect Of 20 Mg Omnitram And 50 Mg Tramadol In Normal Human Subjects Made Cyp2d6 Deficient By Paroxetine
This study evaluates the analgesic effect of Omnitram and tramadol during concurrent administration of paroxetine. Paroxetine administration is expected to diminish the analgesic effect of tramadol, but not Omnitram. Each participant will receive paroxetine before and during treatment with Omnitram, tramadol, and placebo.
Read the detailed description
A randomized, double-blind, placebo-controlled study to investigating the steady-state oral pharmacokinetics and hypoalgesic effects of overencapsulated: 20 mg Omnitram (2x10 mg tablets), 50 mg tramadol (1x50 mg Ultram tablet), and placebo in male and female subjects made CYP2D6 deficient by paroxetine coadministration.
Sixty participants in normal health, 18 to 50 years of age, who meet the entry criteria, will be randomized to one of the three treatments in treatment segment 1. Each arm will ingest three consecutive 20 mg daily doses of paroxetine. Twelve hours after the first paroxetine dose, subjects will be randomized to one of the treatment sequences to ingest a total of 9 doses of Omnitram, tramadol, or placebo (one dose every 6 hours). Immediately before the 9th dose a blood sample will be collected to quantify plasma Omnitram, tramadol, and paroxetine. After the 9th study drug dose, six blood samples will be collected (1.0, 1.5, 2.0, 2.5, 4.0, and 8.0 hours after the 9th dose is administered) to quantify the Omnitram and tramadol. After the 9th dose, pain tolerance will be assessed with a cold pressor test (immersion of hand in ice cold water). Participants will washout for 11-15 days after treatment 1 and treatment 2. The study will analyze treatment side effects, the pharmacokinetics, and pain tolerance.
- Conditions
- Pain
- Being tested
- Omnitram, Tramadol, Placebo
- Keywords
- analgesia, Cytochrome P450 2D6
- Medical subject headings
- Pain, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmnitramDrug
Omnitram tablets overencapsulated
TramadolDrug
Tramadol tablet overencapsulated
PlaceboDrug
Microcrystalline powder overencapsulated
| Study group | Role | What they receive |
|---|---|---|
| Omnitram | Experimental | Oral Omnitram 20 mg (overencapsulated 10 mg tablets) administered every 6 hours for nine doses, coadministered with paroxetine. Receives: Drug: Omnitram |
| Tramadol | Active comparator | Oral tramadol 50 mg (overencapsulated 50 mg tablet) administered every 6 hours for nine doses, coadministered with paroxetine. Receives: Drug: Tramadol |
| Placebo | Placebo comparator | Oral placebo (overencapsulated microcrystalline) administered every 6 hours for nine doses, coadministered with paroxetine. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cold Pressor Test - Cold Water Induced-Pain
The participant immerses a hand in cold water for a maximum of 3 minutes and reports the pain they experience using a "0 (no pain) to 10 (worst pain)" scale. Immersion of hand in ice cold water
Measured: The test is performed on Day 3, shortly after the ninth (final) dose of study drug.
Secondary outcomes (2)
Adverse Events
Adverse events will include: 1) reports by participants; 2) observations by investigators; and 3) abnormal laboratory safety test results.
Measured: Participant report adverse events throughout study enrolment; investigators observe adverse events during all three 3 day inpatient treatment segments; laboratory safety labs are obtained on Day 3 of treatment segment 3 (the final treatment segment).
Steady State Pharmacokinetics
Study drug plasma concentrations are assessed using specimens collected immediately before and after the 9th dose of each treatment.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start31 Oct 2017
- Primary completion15 Dec 2017
- Study completion22 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syntrix Biosystems, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences, DF/Net Rearch, ITT Research Institute
- Responsible party
- Sponsor
- Investigators
- Shawn L Searle, MD, Principal investigator, PRA Health SciencesStuart Kahn, MD, Study director, Syntrix Biosystems
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03312777
- Sponsor's protocol ID
- Omni-Pain-102
- Status last verified
- Dec 2017
- First submitted
- 4 Oct 2017
- Last updated
- 28 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zebala JA, Searle SL, Webster LR, Johnson MS, Schuler AD, Maeda DY, Kahn SJ. Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. J Pain. 2019 Oct;20(10):1218-1235. doi: 10.1016/j.jpain.2019.04.005. Epub 2019 Apr 18.
PubMed 31005596
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Double-Blind, Randomized, Placebo-Controlled, Three Segment Cross-Over Study Investigating Oral Steady-State Pharmacokinetics And Hypoalgesic Effect Of 20 Mg Omnitram And 50 Mg Tramadol In Normal Human Subjects Made Cyp2d6 Deficient By Paroxetine
- ClinicalTrials.gov ID
- NCT03312777
- Acronym / sponsor ID
- Omni-Pain-102
- Conditions
- Pain
- Keywords
- analgesia, Cytochrome P450 2D6
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Syntrix Biosystems, Inc.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences, DF/Net Rearch, ITT Research Institute
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 15 Dec 2017 (actual)
- Study completion
- 22 Dec 2017 (actual)
- First posted
- 18 Oct 2017 (actual)
- 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 evaluates the analgesic effect of Omnitram and tramadol during concurrent administration of paroxetine. Paroxetine administration is expected to diminish the analgesic effect of tramadol, but not Omnitram. Each participant will receive paroxetine before and during treatment with Omnitram, tramadol, and placebo.
Detailed description
A randomized, double-blind, placebo-controlled study to investigating the steady-state oral pharmacokinetics and hypoalgesic effects of overencapsulated: 20 mg Omnitram (2x10 mg tablets), 50 mg tramadol (1x50 mg Ultram tablet), and placebo in male and female subjects made CYP2D6 deficient by paroxetine coadministration.
Sixty participants in normal health, 18 to 50 years of age, who meet the entry criteria, will be randomized to one of the three treatments in treatment segment 1. Each arm will ingest three consecutive 20 mg daily doses of paroxetine. Twelve hours after the first paroxetine dose, subjects will be randomized to one of the treatment sequences to ingest a total of 9 doses of Omnitram, tramadol, or placebo (one dose every 6 hours). Immediately before the 9th dose a blood sample will be collected to quantify plasma Omnitram, tramadol, and paroxetine. After the 9th study drug dose, six blood samples will be collected (1.0, 1.5, 2.0, 2.5, 4.0, and 8.0 hours after the 9th dose is administered) to quantify the Omnitram and tramadol. After the 9th dose, pain tolerance will be assessed with a cold pressor test (immersion of hand in ice cold water). Participants will washout for 11-15 days after treatment 1 and treatment 2. The study will analyze treatment side effects, the pharmacokinetics, and pain tolerance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Omnitram | Experimental | Drug: OmnitramOral Omnitram 20 mg (overencapsulated 10 mg tablets) administered every 6 hours for nine doses, coadministered with paroxetine. |
| Tramadol | Active comparator | Drug: TramadolOral tramadol 50 mg (overencapsulated 50 mg tablet) administered every 6 hours for nine doses, coadministered with paroxetine. |
| Placebo | Placebo comparator | Drug: PlaceboOral placebo (overencapsulated microcrystalline) administered every 6 hours for nine doses, coadministered with paroxetine. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Healthy males and females with normal vital signs: systolic blood pressure > 90 mm Hg and < 140 mm Hg; diastolic blood pressure > 45 mm Hg and < 90 mm Hg; pulse 40 to 100 beats per minute; respiratory rate 10 to 20 breathes per minute.
- Between the ages of 18 and 50 years of age.
- Able and willing to give informed consent
- Able to comply with all study procedures.
- If female, must not be of childbearing potential or must agree to use one or more of the following forms of contraception during screening and for 30 days following study drug administration: hormonal (e.g., oral, transdermal, intravaginal, implant or injection); double barrier (i.e., condom, diaphragm with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); abstinence; or bilateral tubal ligation.
Key exclusion criteria (12 listed)
- Oral temperature > 38°C or history of current illness.
- History of seizures, epilepsy, or recognized increase risk of seizure (e.g., head trauma, metabolic disorders, alcohol or drug withdrawal).
- History of cirrhosis or laboratory evidence of liver disease.
- Use of alcohol within 24 hours of day -1 until the end of the study; and grapefruit, grapefruit-related citrus fruits (e.g., Seville oranges, pomelos), or grapefruit juice or grapefruit-related juices, or other medication, within 7 days of study drug administration and until the end of the study.
- History of previous anaphylaxis, severe allergic reaction to paroxetine, tramadol, codeine, or other opioid drugs.
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 |
|---|---|---|
| OmnitramOmnitram tablets overencapsulated | Drug | Omnitram |
| TramadolTramadol tablet overencapsulated | Drug | Tramadol |
| PlaceboMicrocrystalline powder overencapsulated | Drug | Placebo |
Primary outcome
Cold Pressor Test - Cold Water Induced-Pain
Time frame: The test is performed on Day 3, shortly after the ninth (final) dose of study drug.
The participant immerses a hand in cold water for a maximum of 3 minutes and reports the pain they experience using a "0 (no pain) to 10 (worst pain)" scale. Immersion of hand in ice cold water
2 secondary outcomes
Adverse Events
Time frame: Participant report adverse events throughout study enrolment; investigators observe adverse events during all three 3 day inpatient treatment segments; laboratory safety labs are obtained on Day 3 of treatment segment 3 (the final treatment segment).
Steady State Pharmacokinetics
Time frame: 8 hours
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 28 Dec 2017.
- Derived from this study: PubMed 31005596Zebala JA, Searle SL, Webster LR, Johnson MS, Schuler AD, Maeda DY, Kahn SJ. Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials. J Pain. 2019 Oct;20(10):1218-1235. doi: 10.1016/j.jpain.2019.04.005. Epub 2019 Apr 18.
- Individual participant dataSharing planned: No
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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.
Shawn L Searle, MD principal investigator
PRA Health Sciences
Stuart Kahn, MD study director
Syntrix Biosystems
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 Omnitram and Tramadol in people with Pain, run by Syntrix Biosystems, Inc. at 1 site in United States.
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 19 inclusion and 12 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 28 Dec 2017. 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 United States. 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?
Cold Pressor Test - Cold Water Induced-Pain (time frame: The test is performed on Day 3, shortly after the ninth (final) dose of study drug.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03312777, which also lists 1 linked publication.
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 28 Dec 2017.