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

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

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome; Colonic Diseases; Abdominal Pain; Visceral Pain
• Intervention / Treatment: Drug: Menthae piperitae aetheroleum/peppermint oil (colon-targeted-delivery capsule); Drug: Menthae piperitae aetheroleum/peppermint oil (enteric coated capsule)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 5800
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tempocol-ColoPulse®; 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); 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.; Other Names: Tempocol-ColoPulse®
Active Comparator: Tempocol®; 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); Peppermint oil capsule available as an over the counter prescription drug on the Dutch market.; Other Names: Tempocol® (CBG-rvg number 109856)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: A Masclee, Prof, PhD, MD, Maastricht University Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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;2011(8):CD003460. doi: 10.1002/14651858.CD003460.pub3.
• 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. 2018 Nov;35(11):1965-1978. doi: 10.1007/s12325-018-0802-1. Epub 2018 Oct 4.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: November 11, 2014
• First Submitted That Met QC Criteria: November 13, 2014
• First Posted (Estimate): November 14, 2014

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Menthol; Abdominal pain; Visceral pain; Peppermint oil; Irritable bowel syndrome (IBS); Colonic disease; Volatile oil; Plant oil
• Additional Relevant MeSH Terms: Digestive System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Intestinal Diseases; Nociceptive Pain; Irritable Bowel Syndrome; Abdominal Pain; Colonic Diseases; Visceral Pain; Physiological Effects of Drugs; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Peppermint oil
• Other Study ID Numbers: 50941; 2014-004195-32 (EudraCT Number)