Investigation of Efficacy and Safety of PPC-5650 to Experimental Induced Sensation and Pain in the Rectosigmoid

A Randomized, Double-blind, Cross-over Trial in Patients With Irritable Bowel Syndrome Investigating the Efficacy and Safety of PPC-5650 on Sensation and Pain During Standardized Stimulation of the Rectosigmoid

Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. Patients with IBS visit the doctor more frequently, use more diagnostic tests, consume more medications, miss more workdays, and consume more overall direct costs than patients without IBS. More specific treatment of the localized symptoms of IBS is therefore needed, why the present study will investigate the effect and mechanisms of PPC-5650. PPC-5650 is a new chemical entity that can negatively modulate the activity of Acid sensing ion channels (ASICs). It is a potent low molecular weight inhibitor for this class of ion channels described to date.

It is hypothesized that safety, efficacy and mechanisms of local administration in the rectum of PPC-5650 can be evaluated by use of experimental induced sensation and pain in the rectum.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: PPC-5650; Drug: Placebo

Detailed Description

Clinical pain and especially visceral pain is diffuse and widespread, and normally associated with many autonomic symptoms that may blur the characterization of disease in clinical practice. When treating clinical pain analgesic effects are difficult to evaluate due to a number of factors other than the pain intensity. These modifiers of the effect may include complaints relating to psychological, cognitive and social aspects of the illness, as well as systemic reactions. Hence, any change in these factors will invariably also interfere with pain intensity and pain quality and bias the assessment of analgesics in clinical trials.

Because of the confounders mentioned above, experimental pain models are often advantageous for characterizing analgesics. Basic mechanisms in pain perception, transduction and central processing can also be explored by means of human experimental pain models. These models, when applied to healthy volunteers or to patients, provide an important translational link between preclinical animal testing and human clinical trials. In clear contrast to clinical pain, experimental pain models allow the possibility of controlling the duration, the intensity and the nature of the pain stimulus. As pain is a multidimensional perception it is obvious that the reaction to a single stimulus of a certain modality only represents a limited part of the pain experience and therefore a variety of stimulus modalities are required to mimic the clinical situation. By use of a multi-modal pain model it is possible to induce sensation and pain in the rectum, investigating safety, effect and mechanisms of drugs.

This is an exploratory study investigating effect, mechanisms and safety of PPC-5650 to experimental induced pain in patients with IBS. The study aims to provide data to support further evaluation of PPC-5650 in the gastrointestinal area.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, SE-413 45
    • Department of Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent
• Postmenopausal women or women who have undergone hysterectomy, and males between 18 and 70 years of age
• Pain intensity during pain attack should be >5 on the GSRS questionnaire
• Hypersensitivity within the last 2 years measured with the barostat
• Patients able to co-operate and tolerate the experimental procedures (as assessed in the training visit)
• Patients on stable medication
• Only patients that do not take over the counter medication 24h before the two study sessions

Exclusion Criteria:

• Any history of, or current condition or medication that, as judged by the investigator, may affect gastrointestinal function and the interpretation of the clinical data
• Any clinically relevant abnormal values from the laboratory tests on hematology, clinical chemistry, urine analyses and/or faeces testing, as judged by the investigator.
• Chronic extraintestinal pain dominating the clinical history
• Any known biochemical or structural abnormality of the digestive tract such as gluten enteropathy, bile acid diarrhea, lymphocytic colitis and/or collagenous colitis, Chronic inflammatory bowel diseases, chronic pancreatitis
• Major intra-abdominal surgery; appendectomy and minor laparoscopic gynecological surgery acceptable.
• Any planned surgical intervention within the duration of the trial.
• Any abdominal surgery
• Participation in any other clinical trial within three months prior to the pre-screening visit.
• Alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Solution for administration in the rectum Identical tp active solution but without active drug; Other Names: No other name
ACTIVE_COMPARATOR: PPC-5650	Drug: PPC-5650; Solution for administration in the rectum Single dose of 25µg/ml at a volume of 50ml; Other Names: No other name

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of PPC-5650	Outcome measurements are achieved by use of multimodal pain responses (thermal, mechanical, electrical) in the rectosigmoid.	Change in pain from baseline to 120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of PPC-5650	By recording adverse effects as well as fysiological characters e.g. blood pressure, pulse, ECG is will be possible to assess safety profile of PPC-5650	Change from baseline to 120 minutes
Effect of PPC-5650	Outcome is achieved by measuring pain and sensory responses to experimental induced pain in the rectosigmoid by use of visual analogue scale (VAS) at VAS=1, 3, 5 and 7	Change in pain from baseline to 120 minutes
Central mechanisms	This outcome is done by use of referred pain areas to the experimental induced pain in the rectosigmoid	Change from baseline to 120 minutes
Objective pain	Assessment of objective pain will be done by recording evoked brain potentials to electrical stimulation in the rectosigmoid	Change from baseline to 120 minutes

Collaborators and Investigators

• Sponsor: Aros Pharma ApS
• Investigators: Study Director: Asbjørn M Drewes, Professor, Mech-Sense, Aalborg Hospital, Aalborg, Denmark

Publications and helpful links

Helpful Links

• Information regarding multi-modal probe used for inducing experimental pain in the rectum

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): May 1, 2013
• Study Completion (ACTUAL): May 1, 2013

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (ESTIMATE): October 10, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 21, 2014
• Last Update Submitted That Met QC Criteria: May 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: IBS; Rectum; Experimental pain
• Other Study ID Numbers: Aros-001