PharmacokineticsPhase 1NCT03767036
Administration of Tramadol and Ketorolac Separately and Simultaneously to Assess a Potential Pharmacokinetic Interaction
A Phase 1 study testing Tramadol hydrochloride 25 mg capsule and Ketorolac Tromethamine 10 mg tablet in people with Pharmacokinetics, run by Grünenthal GmbH at 1 site in Mexico.
Trial summary
Tramadol (Tradol) and ketorolac (Dolac) are marketed products to treat acute pain. This study was performed to determine if both medications can be given to a patient simultaneously without a change of the products' bioavailability. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics
- What is being tested?
- Tramadol hydrochloride 25 mg capsule and Ketorolac Tromethamine 10 mg tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteMexico
- Study dates
- 5 Jun 2017to 30 Jun 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participation in the study will be voluntary and according to the guidelines proposed by the Health General Law (from Mexico), and informed consent will be obtained according to the previously mentioned law. In addition, the study will be conducted according to the ethical principles that have their origin in the Declaration of Helsinki, the current Brazilian regulations, and Good Clinical Practice.
- Only healthy volunteers, men and women aged between 18 and 55 years will be included.
- The body mass index must be between 18.0 and 27.0 kilograms per square meter according to the Quetelet index.
- Women of childbearing potential must be willing to use contraceptive methods (including barrier methods, non-hormonal intra-uterine device, or have a preexistent bilateral tubal ligation) or practice abstinence as a form of lifestyle during the conduct of the study.
- Participants must be healthy as determined by the results of a complete clinical history recorded by the clinical investigational site physicians and the results of the laboratory and other complementary diagnostic tests done by a certified clinical laboratory.
- The allowed limits of variation within normal in the screening visit will be: systolic blood pressure (sitting) 90 to 130 millimeters mercury (mmHg), diastolic blood pressure 60 to 89 mmHg, heart rate between 50 and 100 beats per minute and respiratory rate between 12 and 20 breaths per minute according to the current standard operating procedure. Vital signs will be measured after 5 minutes of resting in a sitting position.
Show all 17Show fewer
- Laboratory and other examinations to be conducted for the inclusion of participants will be:
- Complete blood count: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte distribution width, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils.
- Blood chemistry 27 elements: glucose, urea, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, uric acid, cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, atherogenic index, total protein, albumin, globulins, albumin/globulin ratio, total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, total alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, iron, calcium, sodium, potassium, and chloride.
- Urinalysis: Physical examination (color, appearance, density); chemical examination (pH, leukocytes, nitrite, protein, glucose, ketones, bilirubin, urobilinogen, hemoglobin); microscopic examination (leukocytes, erythrocytes, dysmorphic erythrocytes, casts, crystals, squamous epithelial cells, tubular renal cells, mucus, bacteria and yeasts).
- Hepatitis B screening (Antibody to hepatitis B core antigen [Anti-HBc], antibody to hepatitis B surface antigen [HBs-Ab], antibody to hepatitis B surface antigen [Anti-HBs]) and hepatitis C antibodies.
- Human immunodeficiency virus (HIV) test: Antibodies to the human immunodeficiency virus (Anti-HIV 1 and 2).
- Venereal disease research laboratory (VDRL) test.
- Urine drugs of abuse test at the screening visit and at on Day 0 (day prior to the administration of the IMP.
- Alcohol breath test at the screening visit and at on Day 0 (day prior to the administration of the IMP.
- Serum pregnancy test (beta-human chorion gonadotropin [ß-HCG]) at the screening visit and the final evaluation as well as a urine pregnancy test (qualitative) at approximately 12 hours prior to the administration of the IMP.
- 12-lead electrocardiogram (with a validity not older than 3 months).
Who cannot join
- Participants with a history of the following diseases: cardiovascular (congestive heart failure, ischemic heart disease, peripheral arterial disease, high blood pressure), neurologic (epilepsy, non-controlled seizures, cerebrovascular disease), renal (creatinine clearance below 30 milliliters per minute), hepatic (severe hepatic failure, active hepatic disease or transaminase increase that exceeds three times the upper limit of normal), pulmonary, muscular, metabolic (dehydration, hypovolemia, hyperlipidemia, diabetes mellitus), gastrointestinal (intestinal inflammatory disease) including constipation, endocrine, hematopoietic or any type of anemia, mental disease, or other organic abnormalities as well as those participants who have had muscular trauma within 21 days previous to the study will also be excluded.
- Participants who require any kind of medication during the course of the study, apart from the IMP.
- Participants with a history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer, active or recurring gastrointestinal perforation or hemorrhage.
- Current or recent (within 14 days prior to administration of the study medication) use of monoamine oxidase inhibitors (MAOIs).
- Current use of acetylsalicylic, other non-steroidal anti-inflammatory drugs (NSAIDs), pentoxifylline and probenecid.
- Participants with a history of hypersensibility to aspirin and other NSAIDs.
Show all 26Show fewer
- History of major surgeries (cranial surgery, thorax, abdomen or extensive surgeries in extremity requiring the use of general or regional anesthesia and/or respiratory support) within 3 months prior to the study.
- Participants with a history of asthma, acute rhinitis, nasal polyps, angioneurotic edema, urticarial and allergy-type reactions associated with NSAIDs.
- Participants who have been exposed to medications known to be hepatic enzyme inducers or inhibitors within 30 days (or 7 half-lives) prior to the start of the study.
- Participants who have taken any type of medication including vitamin supplements (with or without prescription) or herbal remedies within 30 days (or 7 half-lives) prior to the start of the study.
- Estimated creatinine clearance (CLcr) equal to or below 80 milliliters per minute based on the Cockcroft-Gault formula (for female participants, the result should be multiplied by 0.85): CLcr = (140-age[year])(corporal weight[kg] divided by (72)(creatinine in serum[milligrams per deciliter]). A participant with a creatinine clearance estimated to be 10 percent or less than 80 milliliters per minute can be randomized at the principal investigator's discretion.
- Participants who have been hospitalized for any reason within 6 months prior to the start of the study.
- Participants who have taken IMPs from other investigations within 180 days (6 months) prior to study start.
- Participants with an allergy to the study medication (tramadol or other opioids/ketorolac), any other medication, food, or substance.
- Participants who have consumed alcohol, carbonated beverages and/or beverages that contain methylxanthines (coffee, tea, cocoa, chocolate, mate, cola, etc.), grapefruit juice, or charbroiled foods within 12 hours prior to the start of the hospitalization period as well as participants who have smoked tobacco within 12 hours prior to the study start.
- Participants who have donated or lost more than 450 milliliters (mL) of blood within 60 days prior to study begin.
- Participants with a history of dependence/abuse of alcohol, psychoactive substances within the 2 previous years.
- Participants requiring a special diet for any reason, e.g., vegetarian.
- Participants unable to understand the nature, objectives, and possible consequences of the study.
- Evidence of the participant's uncooperativeness (lack of adherence to the instructions and requirements of the study personnel) during the process of selection for the study.
- Participants with positive test results for drugs of abuse, pregnancy and/or alcohol.
- Participants currently lactating.
- Participants receiving hormonal therapy via any route of administration.
- Participants who are not registered in the Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) webpage.
- Relationship of subordination between the participants and the investigators.
- Sponsor or clinical research institute employees.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Investigación Farmacológica y Biofarmacéutica, S.A.P.I de C.V. (IFaB)
Mexico City, C.P. 14610
About this study
Official title: Single Site Pharmacokinetic Non-interaction Study With Open-label, Randomized, Single-dose, Three-period, Six-sequence, Crossover Design to Compare Tramadol Hydrochloride 25 mg Capsules (Tradol [Trade Mark], Product of Grünenthal Mexico S.A. de C.V.) and Ketorolac Tromethamine 10 mg Tablets (Dolac [Trade Mark], Product of Siegfried Rhein, S.A. de C.V.) Administered Separately and Simultaneously in Healthy Volunteers Under Fasting Conditions
Tramadol (Tradol) and ketorolac (Dolac) are marketed products to treat acute pain. This study was performed to determine if both medications can be given to a patient simultaneously without a change of the products' bioavailability.
Read the detailed description
The primary objective of the study was to compare the bioavailability of tramadol 25 mg and ketorolac 10 mg after oral single-dose administration of the individual components, either separately or simultaneously, in healthy volunteers under fasting conditions, to demonstrate the absence of a pharmacokinetic interaction.
The secondary objective of the study was to evaluate the safety of both drugs when administered separately and simultaneously based on adverse events reported after treatment.
Participants were admitted to the study site for approximately 42 hours (12 hours before and 30 hours after dosing) for each of the 3 treatment periods. A final examination was performed 2 days after completion of the last treatment period.
- Conditions
- Pharmacokinetics
- Being tested
- Tramadol hydrochloride 25 mg capsule, Ketorolac Tromethamine 10 mg tablet
- Keywords
- tramadol, ketorolac, interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tramadol hydrochloride 25 mg capsuleDrug
Also called Tradol (trade mark)
Capsule with tramadol hydrochloride 25 mg; Product of Grünenthal de Mexico S.A. de C.V.
Ketorolac Tromethamine 10 mg tabletDrug
Also called Dolac (trade mark)
Tablet with ketorolac tromethamine 10 mg; Product of Siegfried Rhein, S.A. de C.V., Mexico
| Study group | Role | What they receive |
|---|---|---|
| Tramadol | Active comparator | Each participant received an oral dose of tramadol hydrochloride 25 mg (A1, one capsule) under fasting conditions with 250 milliliters (mL) of water. Receives: Drug: Tramadol hydrochloride 25 mg capsule |
| Ketorolac | Active comparator | Each participant received an oral dose of ketorolac 10 mg (A2, one tablet) under fasting conditions with 250 mL of water. Receives: Drug: Ketorolac Tromethamine 10 mg tablet |
| Tramadol and ketorolac | Experimental | Each participant received an oral dose of tramadol hydrochloride 25 mg and ketorolac 10 mg simultaneously (A3 = one capsule of A1 + one tablet of A2, test medication) under fasting conditions with 250 mL of water. Receives: Drug: Tramadol hydrochloride 25 mg capsule; Drug: Ketorolac Tromethamine 10 mg tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tramadol: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
One blood sample was taken before administration of the investigational medicinal product (IMP) and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of tramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
O-desmethyltramadol: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of O-desmethyltramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Ketorolac: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of ketorolac was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Tramadol: maximum plasma concentration (Cmax)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of tramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
O-desmethyltramadol: maximum plasma concentration (Cmax)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of O-desmethyltramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Ketorolac: maximum plasma concentration (Cmax)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of ketorolac was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Secondary outcomes (3)
Tramadol: time to maximum plasma concentration (tmax)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of tramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The time to maximum tramadol plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
O-desmethyltramadol: time to maximum plasma concentration (tmax)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of O-desmethyltramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The time to maximum O-desmethyltramadol plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Ketorolac: time to maximum plasma concentration (tmax)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of ketorolac was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The time to maximum ketorolac plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2018
- Study start5 Jun 2017
- Primary completion28 Jun 2017
- Study completion30 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies 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
- Model description
- Open-label, randomized, crossover design with three treatment periods and six sequences (A3-A1-A2, A1-A2-A3, A2-A3-A1, A3-A2-A1, A1-A3-A2, A2-A1-A3) with single administration of tramadol (A1), ketorolac (A2) or tramadol and ketorolac (A3). Treatment periods were separated by a washout period of at least 4 days.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grünenthal GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Grünenthal Colombiana S.A.
- Responsible party
- Sponsor
- Investigators
- Grünenthal Study Director, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03767036
- Sponsor's protocol ID
- HP8002-01
- Other IDs
- TRMKTR-01-GRU, 16-CI-16 053 026
- Status last verified
- Dec 2018
- First submitted
- 5 Dec 2018
- Last updated
- 11 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Site Pharmacokinetic Non-interaction Study With Open-label, Randomized, Single-dose, Three-period, Six-sequence, Crossover Design to Compare Tramadol Hydrochloride 25 mg Capsules (Tradol [Trade Mark], Product of Grünenthal Mexico S.A. de C.V.) and Ketorolac Tromethamine 10 mg Tablets (Dolac [Trade Mark], Product of Siegfried Rhein, S.A. de C.V.) Administered Separately and Simultaneously in Healthy Volunteers Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT03767036
- Acronym / sponsor ID
- HP8002-01
- Conditions
- Pharmacokinetics
- Keywords
- tramadol, ketorolac, interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Grünenthal GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Grünenthal Colombiana S.A.
- Study start
- 5 Jun 2017 (actual)
- Primary completion
- 28 Jun 2017 (actual)
- Study completion
- 30 Jun 2017 (actual)
- First posted
- 6 Dec 2018 (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.
Tramadol (Tradol) and ketorolac (Dolac) are marketed products to treat acute pain. This study was performed to determine if both medications can be given to a patient simultaneously without a change of the products' bioavailability.
Detailed description
The primary objective of the study was to compare the bioavailability of tramadol 25 mg and ketorolac 10 mg after oral single-dose administration of the individual components, either separately or simultaneously, in healthy volunteers under fasting conditions, to demonstrate the absence of a pharmacokinetic interaction.
The secondary objective of the study was to evaluate the safety of both drugs when administered separately and simultaneously based on adverse events reported after treatment.
Participants were admitted to the study site for approximately 42 hours (12 hours before and 30 hours after dosing) for each of the 3 treatment periods. A final examination was performed 2 days after completion of the last treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Open-label, randomized, crossover design with three treatment periods and six sequences (A3-A1-A2, A1-A2-A3, A2-A3-A1, A3-A2-A1, A1-A3-A2, A2-A1-A3) with single administration of tramadol (A1), ketorolac (A2) or tramadol and ketorolac (A3). Treatment periods were separated by a washout period of at least 4 days.
| Arm | Type | Receives |
|---|---|---|
| Tramadol | Active comparator | Drug: Tramadol hydrochloride 25 mg capsuleEach participant received an oral dose of tramadol hydrochloride 25 mg (A1, one capsule) under fasting conditions with 250 milliliters (mL) of water. |
| Ketorolac | Active comparator | Drug: Ketorolac Tromethamine 10 mg tabletEach participant received an oral dose of ketorolac 10 mg (A2, one tablet) under fasting conditions with 250 mL of water. |
| Tramadol and ketorolac | Experimental | Drug: Tramadol hydrochloride 25 mg capsule, Drug: Ketorolac Tromethamine 10 mg tabletEach participant received an oral dose of tramadol hydrochloride 25 mg and ketorolac 10 mg simultaneously (A3 = one capsule of A1 + one tablet of A2, test medication) under fasting conditions with 250 mL of water. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Participation in the study will be voluntary and according to the guidelines proposed by the Health General Law (from Mexico), and informed consent will be obtained according to the previously mentioned law. In addition, the study will be conducted according to the ethical principles that have their origin in the Declaration of Helsinki, the current Brazilian regulations, and Good Clinical Practice.
- Only healthy volunteers, men and women aged between 18 and 55 years will be included.
- The body mass index must be between 18.0 and 27.0 kilograms per square meter according to the Quetelet index.
- Women of childbearing potential must be willing to use contraceptive methods (including barrier methods, non-hormonal intra-uterine device, or have a preexistent bilateral tubal ligation) or practice abstinence as a form of lifestyle during the conduct of the study.
- Participants must be healthy as determined by the results of a complete clinical history recorded by the clinical investigational site physicians and the results of the laboratory and other complementary diagnostic tests done by a certified clinical laboratory.
Key exclusion criteria (26 listed)
- Participants with a history of the following diseases: cardiovascular (congestive heart failure, ischemic heart disease, peripheral arterial disease, high blood pressure), neurologic (epilepsy, non-controlled seizures, cerebrovascular disease), renal (creatinine clearance below 30 milliliters per minute), hepatic (severe hepatic failure, active hepatic disease or transaminase increase that exceeds three times the upper limit of normal), pulmonary, muscular, metabolic (dehydration, hypovolemia, hyperlipidemia, diabetes mellitus), gastrointestinal (intestinal inflammatory disease) including constipation, endocrine, hematopoietic or any type of anemia, mental disease, or other organic abnormalities as well as those participants who have had muscular trauma within 21 days previous to the study will also be excluded.
- Participants who require any kind of medication during the course of the study, apart from the IMP.
- Participants with a history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer, active or recurring gastrointestinal perforation or hemorrhage.
- Current or recent (within 14 days prior to administration of the study medication) use of monoamine oxidase inhibitors (MAOIs).
- Current use of acetylsalicylic, other non-steroidal anti-inflammatory drugs (NSAIDs), pentoxifylline and probenecid.
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 |
|---|---|---|
| Tramadol hydrochloride 25 mg capsuleAlso: Tradol (trade mark)Capsule with tramadol hydrochloride 25 mg; Product of Grünenthal de Mexico S.A. de C.V. | Drug | Tramadol, Tramadol and ketorolac |
| Ketorolac Tromethamine 10 mg tabletAlso: Dolac (trade mark)Tablet with ketorolac tromethamine 10 mg; Product of Siegfried Rhein, S.A. de C.V., Mexico | Drug | Ketorolac, Tramadol and ketorolac |
Primary outcome
Tramadol: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
One blood sample was taken before administration of the investigational medicinal product (IMP) and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of tramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
O-desmethyltramadol: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of O-desmethyltramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Ketorolac: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of ketorolac was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Tramadol: maximum plasma concentration (Cmax)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of tramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
O-desmethyltramadol: maximum plasma concentration (Cmax)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of O-desmethyltramadol was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Ketorolac: maximum plasma concentration (Cmax)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
One blood sample was taken before administration of the IMP and one sample at each of the following time points: 0.167, 0.25, 0.333, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 5.0, 7.0, 9.0, 12.0, 18.0, 24.0 and 30.0 hours in each period. The quantification of ketorolac was done using a validated reversed phase high-performance liquid chromatography-tandem mass spectrometry bioanalytical assay. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
3 secondary outcomes
Tramadol: time to maximum plasma concentration (tmax)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
O-desmethyltramadol: time to maximum plasma concentration (tmax)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
Ketorolac: time to maximum plasma concentration (tmax)
Time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)
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 11 Dec 2018.
- Individual participant dataSharing planned: No
Related trials for Pharmacokinetics
RecruitingObservational study
Population Pharmacokinetics of Temocillin in Acute Enterobacterial Pyelonephritis in Children
Pyelonephritis
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
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.
Grünenthal Study Director study director
Grünenthal GmbH
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 Tramadol hydrochloride 25 mg capsule and Ketorolac Tromethamine 10 mg tablet in people with Pharmacokinetics, run by Grünenthal GmbH at 1 site in Mexico.
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 17 inclusion and 26 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 11 Dec 2018. 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 Mexico. 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. 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?
Tramadol: area under the plasma concentration-time curve from 0 to time t (AUC0-t) (time frame: Before IMP administration and up to 30 hours thereafter (20 time points in total)). The study lists 6 primary outcomes in all. 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 11 Dec 2018.