Last updated: 07/16/2024 06:10:15
Evaluation of indomethacin challenge on intestinal permeability using sugar probes in healthy participants
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A three-period cross-over study to evaluate the effect of an indomethacin challenge on intestinal permeability using sugar probes in healthy male and female participants aged 18 to 60 years
Trial description: This will be a placebo-controlled, 3-period cross-over enabling study conducted in healthy male and female participants, aged 18-60 inclusive.The purpose of this study is to estimate permeability of the small intestine in healthy participants following dosing with indomethacin or placebo by measuring the lactulose:rhamnose ratio in the urine. The study will also evaluate the safety of the indomethacin challenge and associated sampling procedures, and the reproducibility of the estimate of small intestinal permeability following dosing with indomethacin or placebo.To allow for the day-to-day variability of the participants’ intestinal permeability, a 3-period cross-over design is used such that each participant will have indomethacin, placebo and a repeat of either placebo or indomethacin in separate periods. Between each study period, there is a washout of a minimum of 7 days to ensure that there is a gap of over 5 half-lives between each period, which in turn prevents carry over effects of indomethacin between periods. Participants will be randomized to receive treatment in following 4 sequences: 1) Placebo: Indomethacin: Indomethacin, 2) Indomethacin: Placebo: Placebo, 3) Placebo: Placebo: Indomethacin, and 4) Indomethacin: Indomethacin: Placebo.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Lactulose: rhamnose ratio (L:R ratio) over 0-5hours (h) in urine
Timeframe: Up to 12 weeks
Secondary outcomes:
Number of participants with adverse events (AEs) related to study procedures and Serious AEs (SAEs)
Timeframe: Up to 13 weeks
Lactulose: rhamnose ratio over 0-5 h in urine over repeat assessments within a participant
Timeframe: Up to 12 weeks
Interventions:
Enrollment:
30
Primary completion date:
2023-10-01
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
healthy volunteers
Product
Not applicable
Collaborators
Not applicable
Study date(s)
October 2022 to August 2023
Type
Interventional
Phase
Not applicable
Participation criteria
Sex
Female & Male
Age
18 - 60 Years
Accepts healthy volunteers
Yes
- Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring [12 lead electrocardiogram (ECGs)].
- Significant history of or current gastrointestinal disorders: including previous gastro-esophageal reflux disease, peptic ulcer disease, previous episode of bleeding from the gastrointestinal tract, inflammatory bowel disease (including microscopic colitis) and irritable bowel syndrome; cardiovascular disease (including thromboembolic disease), respiratory (including those with a history of current or past asthma), hepatic, renal, endocrine (including diabetes and glucose intolerance defined as an Hemoglobin A1C (HbA1c) >5.6%), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data
- History of severe adverse reaction to NSAIDs.
Inclusion and exclusion criteria
Inclusion criteria:
- Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring [12 lead electrocardiogram (ECGs)].
- Able to follow dietary, exercise, and alcohol restrictions during the study
- Body weight greater than (>) 50 kilogram (kg) and body mass index (BMI) within the range 19.5–29.9 kg/meter square (m2) (both inclusive).
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method during the study intervention period (at a minimum until after the last dose of study intervention).
- Capable of giving signed informed consent
Exclusion criteria:
- Significant history of or current gastrointestinal disorders: including previous gastro-esophageal reflux disease, peptic ulcer disease, previous episode of bleeding from the gastrointestinal tract, inflammatory bowel disease (including microscopic colitis) and irritable bowel syndrome; cardiovascular disease (including thromboembolic disease), respiratory (including those with a history of current or past asthma), hepatic, renal, endocrine (including diabetes and glucose intolerance defined as an Hemoglobin A1C (HbA1c) >5.6%), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data
- History of severe adverse reaction to NSAIDs.
- History of severe lactose intolerance or galactosemia.
- Abnormal blood pressure (diastolic >90 millimeters of mercury [mmHg], systolic >140 mmHg).
- Alanine transaminase (ALT) >1.5 x upper limit of normal (ULN).
- Total bilirubin >1.5 x ULN (isolated total bilirubin >1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin less than [<] 35 percent [%]).
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert’s syndrome or asymptomatic gallstones).
- Corrected QT interval (QTc) >480 milliseconds (msec)
- Estimated glomerular filtration rate (eGFR) <90 milliliter (mL)/minutes (min).
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal, and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study intervention, unless in the opinion of the Investigator and the GSK medical monitor, the medication will not interfere with the study procedures or compromise participant safety.
- NSAIDs are not permitted throughout the study and should have not been taken within the 14 days immediately preceding the first dose of study intervention.
- Use of any antibiotic medication is not permitted throughout the study and should not have been taken within the 14 days immediately preceding the first dose of study intervention.
- Use of aspirin is not permitted throughout the study and should not have been taken within the 14 days immediately preceding the first dose of study intervention.
- Presence of hepatitis B surface antigen (HbsAg) at screening or within 3 months prior to first dose of study intervention.
- Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
- Positive hepatitis C Ribonucleic Acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
- Positive pre-study drug/alcohol screen.
- Positive human immunodeficiency virus (HIV) antibody test or within 3 months prior to first dose of study intervention.
- Random blood glucose and HbA1c outside normal laboratory range at screening.
- Current smoker or user of tobacco- or nicotine-containing products (e.g., nicotine patches or vaporizing devices) during or within 6 months prior to study participation.
- Regular use of known drugs of abuse
- Pregnancy and/or lactation.
Trial location(s)
Location
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2GG
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
2023-10-01
Actual study completion date
2023-28-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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