A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00834288

Enrollment

Registered

2009-02-03

Start date

2003-06-30

Completion date

Unknown

Last updated

2012-04-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Subjects, Pharmacokinetics, Bioavailability

Keywords

Healthy subjects, Pharmacokinetics, Bioavailability

Brief summary

The purpose of this study was to compare the pharmacokinetic profiles at steady-state of the test product, Tramadol HCl Once-A-Day (OAD) 200 mg tablets and the reference product, Tramadol HCl 50 mg (IR) tablets (Ortho-McNeil Ultram®). For this purpose, the extent of absorption of tramadol and formation of O-desmethyltramadol (measures of systemic exposure) after multiple administration of 50 mg 6-hourly at 07:30, 13:30, 19:30 and 01:30 (reference product) and 200 mg 24-hourly at 07:30 (test product), were compared.

Interventions

DRUGTramadol HCl

1x200 mg Tramadol HCl OAD tablet daily

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Healthy, non-smoking, male and female subjects between the ages 18 to 55 years (inclusive). * Body mass within 10% of the ideal mass in relation to height and age, according to the BMI * Body mass not less than 70 kg. * Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results with the normal ranges for the relevant laboratory tests (unless the clinical investigator considers the deviation to be irrelevant for the purpose of the study). * Normal ECG and vital signs, or abnormalities which the clinical investigator did not consider a disqualification for participation in the study * Willingness to undergo a pre-study physical examination and pre- and post-study laboratory investigations. * Ability to comprehend and willingness to sign both statements of Informed Consent (for screening and phase-related procedures) * Non-smokers or past smokers who stopped smoking at least three months before entering the study * For females, the following conditions had to be met: * had been postmenopausal for at least two years, or * had been surgically sterilized, or * was of childbearing potential, and all of the following conditions were met: * had a normal menstrual flow within one month before study entry, and * had negative urine pregnancy test at screening and on Day 1 of each study period. If the result of either test was positive, the subject would have been excluded from the study before receiving study medication. * had to agree to use an accepted method of contraception. The subject had to agree to continue with the same method throughout the study. Hormonal contraceptives were not allowed.

Exclusion criteria

* Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements. * History of, or current compulsive alcohol abuse (\> 10 drinks weekly), or regular exposure to other substances of abuse. * Use of any medication, prescribed or over-the-counter, within 2 weeks prior to the first administration of study medication except if this would not have affected the outcome of the study in the opinion of the clinical investigator. Use of hormonal contraceptives agents by females was not allowed. * Participation in another study with an experimental drug within 8 weeks before the first administration of study medication. * Treatment within the previous 3 months with any drug with a well-defined potential for adversely affecting a major organ or system with evidence to this effect. * Major illness during the 3 months before commencement of the screening period. * History of hypersensitivity to the study drug or any related drugs. * History of bronchial asthma. * History of epilepsy. * Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome. * Donation or loss of blood equal to or exceeding 500 ml during the 8 weeks before the first administration of study medication. * Diagnosis of hypotension made during the screening period. * Diagnosis of hypertension made during the screening period or current diagnosis of hypertension. * Resting pulse of \> 100 beats per minutes or \< 45 beats per minutes during the screening period, either supine or standing. * Positive testing for hepatitis B antigen. * Significant liver disease, defined as active hepatitis or elevated liver enzymes (e.g., AST, ALT) \> 3 times the upper boundary of the normal range. * Positive urine screen for drugs of abuse. * Positive urine screen for tobacco use. * History of marijuana, barbiturates, amphetamine, or narcotic abuse within 12 months prior to study start. * Previous participation in a tramadol study. * pregnancy or lactation.

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Plasma Concentration Versus Time Data Pairs at Steady State (AUCss)	24 hours (day 5)	Area under the plasma concentration versus time data pairs over 24 hours (24h) at steady state, on day 5. ss = steady state. AUCss is also known as AUCtau.

Secondary

Measure	Time frame	Description
Minimum Plasma Concentration at Steady State(Cmin,ss)	24 hours (day 5)	Minimum plasma concentration over 24 hours (24h) at steady state on day 5. ss = steady state.
Time to Peak Exposure (Tmax)	24 hours (day 5)	Time to peak exposure over 24 hours (24h) at steady state on day 5.
Percentage Peak-trough Fluctuation (% PTF)	24 hours (day 5)	Percentage peak-trough fluctuation over 24 hours (24h) at steady state on day 5. Percent peak-to-trough fluctuation is calculated as (Cmax - Cmin)/Cav\*100, where Cmax is the maximum observed concentration, Cmin is the minimum observed concentration and Cav is the average concentration over 24 hours (where Cav = AUCss/24).
Maximum Plasma Concentration at Steady State(Cmax,ss)	24 hours (day 5)	Maximum plasma concentration over 24 hours (24h) at steady state, on day 5. ss = steady state.
Half-value Duration (HVD)	24 hours (day 5)	Time over which plasma concentrations were above one half Cmax on day 5. 24h = 24 hours.
Plateau Time (T75%Cmax)	24 hours (day 5)	Time over which plasma concentrations were above 75% Cmax on day 5. 24h = 24 hours.
Percentage Swing	24 hours (day 5)	Percentage swing is a pharmacokinetic parameter recommended by the FDA for submission and is calculated as follows:((Cmax,ss - Cmin,ss)/Cmin,ss)\*100. It was calculated over 24 hours on day 5. Where: Cmax,ss = Maximum concentration at steady state; Cmin,ss = Minimum concentration at steady state.

Participant flow

Participants by arm

Arm	Count
Test (Tramadol HCl OAD 200 mg) First 1 x 200 mg Tramadol OAD (Once-A-Day) Tablet Daily test product dosed in first period followed by Tramadol IR (Ultram®) 50 mg 6-hourly) reference product dosed in the second period. The two treatment phases each started with a run-in period of 4 days (Days 1 to 4), a profile period and clinic stay of 3 days (Days 5 to 7) (clinic days and observation period) and a drug-free period of 16 days between treatment phases (Day 7 of Treatment phase I until Day 1 of the run-in period of Treatment phase II).	13
Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First 1 x 50 mg Tramadol HCl IR (Ultram®) Tablet 6-Hourly reference product dosed in first period followed by Tramadol OAD (Once-A-Day) Tablet Daily test product dosed in the second period. The two treatment phases each started with a run-in period of 4 days (Days 1 to 4), a profile period and clinic stay of 3 days (Days 5 to 7) (clinic days and observation period) and a drug-free period of 16 days between treatment phases (Day 7 of Treatment phase I until Day 1 of the run-in period of Treatment phase II). IR = Immediate Release.	13
Total	26

Baseline characteristics

Characteristic	Test (Tramadol HCl OAD 200 mg) First	Reference (Tramadol IR (Ultram®) 50 mg 6-hourly) First	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0.0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0.0 Participants
Age, Categorical Between 18 and 65 years	13 Participants	13 Participants	26.0 Participants
Sex: Female, Male Female	2 Participants	2 Participants	4.0 Participants
Sex: Female, Male Male	11 Participants	11 Participants	22.0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	12 / 26	10 / 26
serious Total, serious adverse events	0 / 26	0 / 26

Arm	Measure	Value (MEDIAN)
Tramadol HCl OAD 200 mg	Time to Peak Exposure (Tmax)	4 hours
Tramadol IR (Ultram®) 50 mg 6-hourly	Time to Peak Exposure (Tmax)	1 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Area Under the Plasma Concentration Versus Time Data Pairs at Steady State (AUCss)

Half-value Duration (HVD)

Maximum Plasma Concentration at Steady State(Cmax,ss)

Minimum Plasma Concentration at Steady State(Cmin,ss)

Percentage Peak-trough Fluctuation (% PTF)

Percentage Swing

Plateau Time (T75%Cmax)

Time to Peak Exposure (Tmax)