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

Irritable Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02291445
• Other study ID #: 50941
• Secondary ID: 2014-004195-32
• Status: Completed
• Phase: Phase 2
• Start date: March 2015
• Est. completion date: September 2015

Study information

• Verified date: July 2015
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Abdominal Pain
• Colonic Diseases
• Irritable Bowel Syndrome
• Visceral Pain

Intervention

Drug:
• Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)
Peppermint oil capsule available as an over the counter prescription drug on the Dutch market.
• Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule)
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.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (5)

Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014 Jul;48(6):505-12. doi: 10.1097/MCG.0b013e3182a88357. Review. — View Citation

Maurer JM, Schellekens RC, van Rieke HM, Stellaard F, Wutzke KD, Buurman DJ, Dijkstra G, Woerdenbag HJ, Frijlink HW, Kosterink JG. ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability. J Control Release. 2013 Dec 28;172(3):618-24. doi: 10.1016/j.jconrel.2013.09.021. Epub 2013 Oct 2. — View Citation

Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011 Aug 10;(8):CD003460. doi: 10.1002/14651858.CD003460.pub3. Review. — View Citation

Schellekens RC, Stellaard F, Olsder GG, Woerdenbag HJ, Frijlink HW, Kosterink JG. Oral ileocolonic drug delivery by the colopulse-system: a bioavailability study in healthy volunteers. J Control Release. 2010 Sep 15;146(3):334-40. doi: 10.1016/j.jconrel.2010.05.028. Epub 2010 May 31. — View Citation

Weerts ZZRM, Keszthelyi D, Vork L, Aendekerk NCP, Frijlink HW, Brouwers JRBJ, Neef C, Jonkers DMAE, Masclee AAM. A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable Bowel Syndrome: A Phase I Study in Healthy Volunteers. Adv Ther. — View Citation

Outcome

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