To Determine Blood Concentrations of Ibuprofen and Caffeine in a Tablet Against Ibuprofen Alone From Another Tablet

A Single Center, Single Dose, Open Label, Randomized, Two Period, Two Sequence Crossover Study to Evaluate the Relative Bioavailibility of Ibuprofen From a Fixed-dose Combination Tablet Containing Ibuprofen 400 mg and Caffeine 100 mg and a Tablet of Ibuprofen 400 mg in at Least 30 Healthy Males and Females Under Fed Conditions

The objective of the trial is to compare to combination of 400 mg ibuprofen and 100 mg caffeine against 400 mg ibuprofen alone under fed conditions

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Caffeine; Drug: Ibuprofen

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Bloemfontein, South Africa
    • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Healthy males and females, 18 to 50 years (inclusive) at time of screening.
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).
• Body mass not less than 50 kg.
• Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the PI considers the deviation to be irrelevant for the purpose of the study.
• Non-smokers and mild or moderate smokers (<= 10 cigarettes or pipes per day). Further inclusion criteria apply

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.
• Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females. One unit is equal to beer [200 mL/10 ounces], wine [100 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
• Regular exposure to substances of abuse (other than alcohol) within the past year.
• Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks before the first administration of IMP except if this will not affect the outcome of the study in the opinion of the PI. In this study the concomitant use of hormonal contraceptives is allowed.
• Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for anti-bodies or insulin), whichever is the longer) before administration of IMP in this study, at the discretion of the PI.
• Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
• History of hypersensitivity or allergy (angioedema or urticaria) to the IMP or its excipients or any related medication (Aspirin or any other NSAID).
• 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 minute or < 40 beats per minute during the screening period, either supine or standing.
• Renal impairment.
• Positive urine screen for drugs of abuse. In case of a positive result the urine screen for drugs of abuse may be repeated once at the discretion of the PI.

Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ibuprofen	Drug: Ibuprofen
EXPERIMENTAL: Ibuprofen and Caffeine	Drug: Caffeine; Drug: Ibuprofen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of S-ibuprofen	This outcome measure presents the maximum observed concentration (Cmax) of S-ibuprofen in plasma obtained directly from the concentration-time data.	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
Cmax of R-ibuprofen	This outcome measure presents the Cmax of R-ibuprofen in plasma obtained directly from the concentration-time data.	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
Cmax of Ibuprofen	This outcome measure presents the Cmax of ibuprofen in plasma obtained directly from the concentration-time data.	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, From Time Zero to t (AUC0-t)	This outcome measure presents the area under the plasma concentration of S-ibuprofen versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC0-t).	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
AUC0-t of R-ibuprofen	This outcome measure presents the area under the plasma concentration of R-ibuprofen versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC0-t).	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
AUC0-t of Ibuprofen	This outcome measure presents the area under the plasma concentration of ibuprofen versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC0-t).	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, With Extrapolation to Infinity (AUC0-INF)	This outcome measure presents the area under the plasma concentration of S-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
AUC0-INF of R-ibuprofen	This outcome measure presents the area under the plasma concentration of R-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose
AUC0-INF of Ibuprofen	This outcome measure presents the area under the plasma concentration of ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).	Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 10, 2015
• First Posted (ESTIMATE): December 14, 2015

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; 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; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Ibuprofen; Caffeine
• Other Study ID Numbers: 1335.3