Comparing a 182mg Colon-targeted-delivery Peppermint Oil Capsule (Tempocol-ColoPulse®) and a 182mg Enteric-coated Peppermint Oil Capsule (Tempocol®), a Pharmacokinetic Study

Study Overview
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Brief Summary
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This is a pilot study to compare the relative bioavailability between two peppermint oil formulations, namely a ileocolonic release peppermint oil and an small intestinal release peppermint oil (Tempocol®). This study is conducted as part of a future multicenter randomized controlled trial that will assess the therapeutic effect of the new peppermint oil formulation in IBS patients.

Detailed Description
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Rationale: Peppermint oil has shown to be effective in the treatment of IBS symptoms in several meta-analyses. However, the level of evidence is moderate and peppermint oil remains relatively under-used in IBS. Therefore the investigators plan to conduct a multicenter randomized controlled trial to investigate the possible beneficial effects of peppermint oil in IBS. To improve efficacy and to reduce side effects, the investigators aim to study the use of a new peppermint oil formulation that will slowly release the oil in the (ileo-) colonic region specifically. In order to demonstrate differences in pharmacokinetics, the subsidizing party, ZonMW, requested an additional pilot study (described in the present protocol) in which the investigators will investigate surrogate markers for local colon bioavailability, tolerability and side effects of the new ileocolonic release PO. Study design: a randomized, double blind, two-period, two-treatment crossover study with a wash out period of at least 14 days. Intervention: All study volunteers will receive a single dose of 182mg of both ileocolonic release peppermint oil and small intestinal release peppermint oil, each on a different test day. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects may be confronted with certain inconveniences and minor risks. They are required to visit the MUMC+ 5 times, once for the screening and two times per test day for various non-invasive measurements (questionnaires, blood pressure and heart-rate measurement, urine and fecal sampling, pregnancy test in women in fertile ages, general physical exam) as well as for minor invasive venous blood sampling, after which a small haematoma can occur. Total time investment is +/- 30 hours, subjects will not benefit from participation.

Official Title
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A Randomized, Double Blind, Single Dose, Two Treatment, Two Period Crossover Pharmacokinetic Study Comparing a 182mg Colon-targeted-delivery Peppermint Oil Capsule (Tempocol-ColoPulse®) and a 182mg Enteric-coated Peppermint Oil Capsule (Tempocol®) in Healthy Volunteers

Conditions
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Irritable Bowel Syndrome, Abdominal Pain, Colonic Diseases, Visceral Pain

Intervention / Treatment
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* Drug: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)
* Drug: Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Based on medical history and previous examination, no gastrointestinal complaints can be defined Age between 18 and 65 years BMI between 18 and 25 kg/m2 and a weight of at least 50 kilograms Women in fertile age (<55 years old) must use contraception or be postmenopausal for at least two years Exclusion Criteria: History of severe or chronic cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol Use of medication, including vitamin and iron supplementation, except oral contraceptives, within 14 days prior to start of the study Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgment of the principle investigator) Dieting (for example lactose-free, gluten-free, caloric-restrictive, vegetarian or vegan, macrobiotic diet) Pregnancy, lactation High alcohol consumption (>15 alcoholic consumptions per week) Smoking/ Using drugs of abuse Self-admitted HIV-positive state Known allergic reaction to peppermint High intake of caffeine (>8 cups coffee a day)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tempocol-ColoPulse®<br>Tempocol-ColoPulse® is a colon-targeted-delivery peppermint oil capsule that will deliver peppermint oil in the (ileo-) colonic region specifically. | Drug: Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)<br>* Peppermint oil capsule with a coating developed according to the ColoPulse® technology, ensuring a pulsatile and therefore slower release in a lower part of the intestinal tract compared to Tempocol, namely in the (ileo-)colonic region.<br>* Other names: Tempocol-ColoPulse®;|
| Active Comparator: Tempocol®<br>Tempocol® is an enteric-coated peppermint oil capsule that delivers peppermint oil in the upper small intestine. | Drug: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)<br>* Peppermint oil capsule available as an over the counter prescription drug on the Dutch market.<br>* Other names: Tempocol® (CBG-rvg number 109856);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-max | Time to reach maximum menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) concentration in plasma | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-max | Menthol-glucuronide (main constituent of peppermint oil after conversion by the liver) peak plasma concentrations | 24 hours | 
| T-lag | Time until a measurable plasma concentration of menthol-glucuronide occurs after oral administration of peppermint oil (45ug/L) | 24 hours | 
| AUC | Area under the plasma concentration-time curve from t=0 hrs until t=24 hrs. | 24 hours | 
| T1/2 | elimination half-life; time required for the plasma concentration of menthol-glucuronide to reach half of its original value. | 24 hours | 
| Menthol-glucuronide Urine Exretion Time Curve |  | 24 hours | 
| L-Menthol Concentration in Feces |  | +/- 24 hours | 
| Difference in Total Number of Side Effects Per Time Point. |  | 24 hours | 
| Tolerability Assessed by Heart Rate, Blood Pressure and Reported Side Effects | Assessed by heart rate, blood pressure and reported side effects. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peppermint oil, Menthol, Volatile oil, Plant oil, Visceral pain, Abdominal pain, Irritable bowel syndrome (IBS), Colonic disease