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Gamma Scintigraphy Study to Investigate Tablet Disintegration in Healthy Volunteers.

Registration Number
NCT03497715
Lead Sponsor
Reckitt Benckiser Healthcare (UK) Limited
Brief Summary

The study will be an adaptive, 2 part, single dose, 5-way crossover gamma scintigraphy study in healthy subjects, to investigate the rate and site of tablet disintegration of various forms of Ibuprofen.

Detailed Description

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and anti-pyretic properties. There are now a wide variety of formulations of ibuprofen available on market in which the active ingredient, ibuprofen, is either as the free acid, salt or salt in situ. As a result of differences between these formulations, differences in absorption and time to effectiveness are achieved. Rates of absorption are commonly assessed using pharmacokinetic (PK) studies, where the time taken for therapeutic plasma concentration levels to be reached can be determined, with associated absorption profiles being generated.

Before absorption can occur the product must disintegrate in the stomach and empty into the small intestine. Gamma scintigraphy may be used to assess the disintegration rate (of tablets/capsules/caplets) by acquiring images of the investigational medicinal product (IMP) in vivo. Through the use of radiolabelled dosage forms, it enables the visualisation of key stages preceding absorption, including tablet disintegration and the rate of gastric emptying. The assessment of these stages, which are required prior to absorption in the small intestine, may be useful in gaining an understanding of the differences between the dosage forms. The main purpose of this study is to visualise and determine the rate of disintegration and subsequent availability for absorption of different ibuprofen formulations, by gamma scintigraphy.

The study will be conducted in two parts. Part 1 will be conducted as a pilot phase where each subject will receive all 5 IMPs over 5 treatment visits (one IMP/visit).

The data generated in Part 1 will be assessed and used to determine whether to continue to Part 2 as planned, continue to Part 2 with adaptations or stop the study. Adaptations may involve altering the radiolabelling procedure and/or the gamma scintigraphy procedure and/or associated time-points and/or redefining primary/secondary endpoints and statistical analyses.

Recruitment & Eligibility

Status
TERMINATED
Sex
Male
Target Recruitment
6
Inclusion Criteria
  1. Age: > 18 to < 50 years.
  2. Sex: Male.
  3. Status: Healthy volunteers.
Exclusion Criteria
  1. A history of significant disease of any body-system.
  2. Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.
  3. A history of allergy or intolerance (including angio-oedema, urticaria, bronchospasm and rhinitis) related to treatment with ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs) or the excipients of the formulations.
  4. A history of peptic or duodenal ulcers or gastro-intestinal bleed or upper gastrointestinal bleed, or other significant gastro-intestinal disorders.
  5. A history of frequent dyspepsia, e.g., heartburn or indigestion.
  6. A history of migraine.
  7. A history of psychotic illness, attempted suicide or parasuicide.
  8. Current smokers and ex-smokers who have smoked within 6 months.
  9. A history of drug abuse (including alcohol).
  10. High consumption of stimulating drinks (coffee, tea, cola, energy drinks etc.; total caffeine intake per day above 300 mg (1 cup of coffee equates to 50 mg).
  11. Those with positive drugs of abuse screen including alcohol on any occasion throughout the study.
  12. Ingestion of a prescribed drug at any time in the 14 days before dosing with study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers during the previous month (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.).
  13. Ingestion of an over-the-counter preparation within 7 days before dosing with study medication, including herbal medications, vitamin/fish oil supplements, ibuprofen and other NSAIDs and paracetamol.
  14. Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen.
  15. Those unable in the opinion of the Investigator to comply fully with the study requirements.
  16. Those who are unwilling to consume gelatin of animal origin.
  17. Those previously randomised into this study.
  18. Employee at study site.
  19. Partner or first degree relative of the investigator
  20. Those who have participated in a clinical trial in the previous 12 weeks.
  21. Participation in a study in which radioisotopes were administered or in which subjects were exposed to any radiation (e.g. x-rays, handling of radiolabelled materials) other than normal background radiation within the 12 months before the screening visit.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Experimental 1Ibuprofen (Wockhardt)Treatment order: Ibuprofen liquid capsules, Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen (Wockhardt)
Experimental 3Ibuprofen SodiumTreatment order: Ibuprofen liquid capsules, Ibuprofen (Nurofen)1, Ibuprofen sodium, Ibuprofen (Wockhardt), Ibuprofen lysine
Experimental 2Ibuprofen SodiumTreatment order: Ibuprofen lysine, Ibuprofen (Wockhardt), Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen liquid capsules
Experimental 3Ibuprofen (Wockhardt)Treatment order: Ibuprofen liquid capsules, Ibuprofen (Nurofen)1, Ibuprofen sodium, Ibuprofen (Wockhardt), Ibuprofen lysine
Experimental 3IbuprofenTreatment order: Ibuprofen liquid capsules, Ibuprofen (Nurofen)1, Ibuprofen sodium, Ibuprofen (Wockhardt), Ibuprofen lysine
Experimental 1IbuprofenTreatment order: Ibuprofen liquid capsules, Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen (Wockhardt)
Experimental 3Ibuprofen lysineTreatment order: Ibuprofen liquid capsules, Ibuprofen (Nurofen)1, Ibuprofen sodium, Ibuprofen (Wockhardt), Ibuprofen lysine
Experimental 3Ibuprofen (Nurofen)Treatment order: Ibuprofen liquid capsules, Ibuprofen (Nurofen)1, Ibuprofen sodium, Ibuprofen (Wockhardt), Ibuprofen lysine
Experimental 1Ibuprofen SodiumTreatment order: Ibuprofen liquid capsules, Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen (Wockhardt)
Experimental 1Ibuprofen (Nurofen)Treatment order: Ibuprofen liquid capsules, Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen (Wockhardt)
Experimental 2Ibuprofen (Nurofen)Treatment order: Ibuprofen lysine, Ibuprofen (Wockhardt), Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen liquid capsules
Experimental 1Ibuprofen lysineTreatment order: Ibuprofen liquid capsules, Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen (Wockhardt)
Experimental 2Ibuprofen (Wockhardt)Treatment order: Ibuprofen lysine, Ibuprofen (Wockhardt), Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen liquid capsules
Experimental 4IbuprofenTreatment order: Ibuprofen (Wockhardt), Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen liquid capsules, Ibuprofen sodium
Experimental 4Ibuprofen (Nurofen)Treatment order: Ibuprofen (Wockhardt), Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen liquid capsules, Ibuprofen sodium
Experimental 4Ibuprofen (Wockhardt)Treatment order: Ibuprofen (Wockhardt), Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen liquid capsules, Ibuprofen sodium
Experimental 4Ibuprofen lysineTreatment order: Ibuprofen (Wockhardt), Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen liquid capsules, Ibuprofen sodium
Experimental 4Ibuprofen SodiumTreatment order: Ibuprofen (Wockhardt), Ibuprofen (Nurofen), Ibuprofen lysine, Ibuprofen liquid capsules, Ibuprofen sodium
Experimental 2Ibuprofen lysineTreatment order: Ibuprofen lysine, Ibuprofen (Wockhardt), Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen liquid capsules
Experimental 2IbuprofenTreatment order: Ibuprofen lysine, Ibuprofen (Wockhardt), Ibuprofen sodium, Ibuprofen (Nurofen), Ibuprofen liquid capsules
Primary Outcome Measures
NameTimeMethod
Radioactive counts3 hours

radioactivity counts as determined by gamma scintigraphy imaging

Secondary Outcome Measures
NameTimeMethod
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