- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03766984
Pharmacokinetic Non-interaction Study With a Fixed-dose Combination Tablet With Tramadol and Diclofenac
Study of Non-pharmacokinetic Interaction Between Diclofenac 25 mg and 25 mg Tramadol With the Fixed-dose Combination Tablets of the Two Drugs Administered to Healthy Subjects of Both Genders in Fasting State
Study Overview
Status
Conditions
Detailed Description
After a screening period of about 2 weeks, 36 eligible healthy men and women were randomly allocated to receive 3 sequential treatments in the following order:
- a single dose of diclofenac followed by a single dose of the fixed-dose combination of diclofenac/tramadol followed by a single dose of tramadol
- a single dose of tramadol followed by a single dose of the fixed-dose combination of diclofenac/tramadol followed by a single dose of diclofenac.
There were washout periods of 7 days between treatments.
Sixteen blood samples were collected per participant: at pre-dose and 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 36 hours after administration of each of the study drugs.
The pharmacokinetic parameters and relative bioavailabilities of diclofenac and tramadol (and of the tramadol metabolite M1) were determined for the new fixed-dose combination product and were compared to the single compound reference products.
Furthermore, the safety (frequency of adverse events) and tolerability of the new fixed-dose combination of diclofenac 25 mg and 25 mg tramadol in healthy men and women was assessed.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Mexico City, Mexico, CP 09360
- Clinical Unit of Biodextra, S.A. de C.V.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Man or woman between 18 and 55 years of age.
- Women with use of a barrier method as a contraceptive.
- Body mass index equal to or above 18.0 and equal to or less than 27.0 kilograms per square meter.
- Clinically healthy. If the clinical history, the registration of vital signs and the physical examination did not show abnormal deviations that avoid their participation in a clinical study.
- Without a history of allergic reactions to the study drug.
- Stable vital signs during the selection (heart rate, respiratory rate, blood pressure at rest and axillary body temperature).
- Laboratory studies: complete blood count, blood chemistry of 24 items, urinalysis, anti-human immunodeficiency virus (HIV) 1, anti-HIV2, anti-hepatitis B surface antigen (HBs) and anti-hepatitis C virus (HCVs) antibodies, and serologic test for syphilis [Venereal Disease Research Laboratory test]) within normal ranges according to the reference laboratory, or that the deviations are not clinically significant. If the deviation has no clinical significance, it may be justified the inclusion of the participant to the clinical study. The age of the report of the clinical laboratory studies must not be greater than 3 months.
- Electrocardiogram (ECG) with no pathological alterations, with validity of no more than 3 months.
- The participant accepts the restrictions and indications described in the protocol and internal regulations.
- The participant has read and understood the relevant aspects of the clinical study and gives its authorization for participation by signing the informed consent form before inclusion on the clinical study and performing any procedure.
Exclusion Criteria:
- Findings in the clinical history, vital signs and/or physical examination that show abnormal conditions of the general state of health of the participant that avoid its participation in a clinical study.
- Recent exposure to the study drug between the 30 days prior or any other medication by prescription or self consumed between the 14 days prior to the start of the study, or that do not accept to avoid its consumption during the course of the study.
- Surgery during the 30 days prior to the start of the study.
- Suspicion or evidence of infection by Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV).
- Serologic test for syphilis (Venereal Disease Research Laboratory test) positive.
- Known hypersensitivity to any medication.
- Blood donation equal to or above 1 unit (0.5 liters) during the 30 days prior to the selection.
- Participants who have special food requirements or food restrictions.
- Women in the breastfeeding period and/or pregnant.
- Positive results in the qualitative test of pregnancy in urine (only women).
- Positive result in the qualitative detection of drugs of abuse.
- Participation in a clinical study Phase 1, 2 or 3 or bioavailability/ bioequivalence studies during the 3 months previous to the selection.
- The participant does not give his or her authorization to participate in the study through the signing of an informed consent, or is not willing to follow the indications and/or restrictions of the protocol and rules of the procedure.
- The participant is vulnerable or potentially vulnerable by which cannot freely express his/her consent by subordination of the principal investigator or by coercion of any third party.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Diclofenac 25 mg
Participants receive 1 tablet of diclofenac sodium 25 mg with 250 milliliters of purified water.
|
Diclofenac sodium 25 mg Tablets (Laboratorios Tecnandina S.A., Ecuador)
|
Experimental: Tramadol 25 mg
Participants receive 1 tablet of tramadol hydrochloride 25 mg with 250 milliliters of purified water.
|
Tramadol hydrochloride 25 mg Tablets (Laboratorios Tecnandina S.A., Ecuador)
|
Experimental: Diclofenac/Tramadol 25 mg/25 mg FDC
Participants receive 1 fixed-dose combination tablet of diclofenac sodium 25 mg/tramadol hydrochloride 25 mg with 250 milliliters of purified water.
|
Fixed-dose combination tablet containing diclofenac sodium 25 mg and tramadol hydrochloride 25 mg (Laboratorios Tecnandina S.A., Ecuador)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum plasma concentration (Cmax) of diclofenac
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Diclofenac concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Maximum plasma concentration (Cmax) of tramadol
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tramadol concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Area under the plasma concentration curve from the administration until the time t (AUC0-t) of diclofenac
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Diclofenac concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Area under the plasma concentration curve from the administration until the time t (AUC0-t) of tramadol
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tramadol concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum plasma concentration (Cmax) of tramadol metabolite M1
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tramadol M1 concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Area under the plasma concentration curve from the administration until the time t (AUC0-t) of tramadol metabolite M1
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tramadol M1 concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of tramadol
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tramadol concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of tramadol metabolite M1
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tramadol M1 concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Area under the plasma concentration curve from 0 to infinity (AUC0-inf) of diclofenac
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Diclofenac concentrations were determined using validated analytical methods.
|
From pre-dose to 36 hours post-dose
|
Time to maximum plasma concentration (Tmax) for tramadol
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tmax was calculated based on Cmax data for tramadol.
|
From pre-dose to 36 hours post-dose
|
Time to maximum plasma concentration (Tmax) for tramadol metabolite M1
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tmax was calculated based on Cmax data for tramadol M1.
|
From pre-dose to 36 hours post-dose
|
Time to maximum plasma concentration (Tmax) for diclofenac
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
Tmax was calculated based on Cmax data for diclofenac
|
From pre-dose to 36 hours post-dose
|
Elimination half life (t half) for tramadol
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
t half was calculated based on plasma concentration data for tramadol.
|
From pre-dose to 36 hours post-dose
|
Elimination half life (t half) for tramadol metabolite M1
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
T half was calculated based on plasma concentration data for tramadol M1.
|
From pre-dose to 36 hours post-dose
|
Elimination half life (t half) for diclofenac
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
t half was calculated based on plasma concentration data for diclofenac.
|
From pre-dose to 36 hours post-dose
|
Elimination rate constant (KE) for tramadol
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
KE will be calculated based on the plasma concentrations for tramadol.
|
From pre-dose to 36 hours post-dose
|
Elimination rate constant (KE) for tramadol metabolite M1
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
KE was calculated based on the plasma concentrations for tramadol M1.
|
From pre-dose to 36 hours post-dose
|
Elimination rate constant (KE) for diclofenac
Time Frame: From pre-dose to 36 hours post-dose
|
16 plasma samples were collected from pre-dose to 36 hours post-dose.
KE will be calculated based on the plasma concentrations for diclofenac.
|
From pre-dose to 36 hours post-dose
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Analgesics, Opioid
- Narcotics
- Diclofenac
- Tramadol
Other Study ID Numbers
- DCLF/TRMD-GRNN-01
- HP8001-01 (Other Identifier: Grünenthal)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pharmacokinetics
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Subjects | Pharmacokinetics of Isavuconazole | Pharmacokinetics of Methotrexate | Pharmacokinetics of 7-hydroxymethotrexateUnited States
-
Astellas Pharma IncCompletedHealthy | Pharmacokinetics of ASP1941 | Pharmacokinetics of MitiglinideJapan
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Volunteers | Pharmacokinetics of Isavuconazole | Pharmacokinetics of MethadoneUnited States
-
Astellas Pharma IncBasilea PharmaceuticaCompletedHealthy Volunteers | Pharmacokinetics of Isavuconazole | Pharmacokinetics of MidazolamUnited States
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Volunteers | Pharmacokinetics of Isavuconazole | Pharmacokinetics of DigoxinUnited States
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Volunteers | Pharmacokinetics of Isavuconazole | Pharmacokinetics of BupropionUnited States
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Subjects | Pharmacokinetics of Isavuconazole | Pharmacokinetics of SirolimusUnited States
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Volunteers | Pharmacokinetics of Isavuconazole | Pharmacokinetics of AtorvastatinUnited States
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Subjects | Pharmacokinetics of Caffeine | Pharmacokinetics of RepaglinideUnited States
-
Astellas Pharma Global Development, Inc.Basilea Pharmaceutica International LtdCompletedHealthy Subjects | Pharmacokinetics of Isavuconazole | Pharmacokinetics of MetforminUnited States
Clinical Trials on Diclofenac sodium 25 mg
-
University of EdinburghKidney Cancer UKTerminatedRenal Transplant Rejection | Renal Transplant FailureUnited Kingdom
-
Instituto Nacional de Cardiologia Ignacio ChavezNot yet recruitingSTEMI | No-Reflow Phenomenon
-
Javelin PharmaceuticalsCompleted
-
Zydus Lifesciences LimitedRecruitingAmyotrophic Lateral SclerosisIndia
-
ViiV HealthcareGlaxoSmithKline; Janssen PharmaceuticalsCompletedInfection, Human Immunodeficiency VirusUnited States
-
MallinckrodtCompleted
-
University of Sao Paulo General HospitalRecruitingCoronary Artery Disease | Diabetes Mellitus, Type 2 | Acute Kidney Injury | Coronary Artery Bypass SurgeryBrazil
-
National Taiwan University HospitalShin Kong Wu Ho-Su Memorial HospitalNot yet recruitingHeart Failure With Preserved Ejection Fraction | End Stage Renal Disease on Dialysis
-
Aires Pharmaceuticals, Inc.CompletedPulmonary Arterial Hypertension | Pulmonary HypertensionUnited States
-
Idorsia Pharmaceuticals Ltd.CompletedHepatic ImpairmentSwitzerland