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PainPhase 1NCT02276768

Study on Analgesia of GIC-1001 & GIC-1002 on Visceral Pain, Rectal Sensory Threshold Using the Barostat Method

A Phase 1 study testing GIC-1001 375 mg TID, GIC-1001 500 mg TID and GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID) in people with Pain and Cancer, run by gicare Pharma Inc. at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study evaluates colonic analgesia by comparing two novel formulations, GIC-1001 and GIC-1002 with placebo using a barostat distender. The healthy male and female volunteers randomized to one of 5 possible treatments will be exposed to rectal distension following a 3-day treatment TID. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Pain, Cancer, Colonic Disease
What is being tested?
GIC-1001 375 mg TID, GIC-1001 500 mg TID and GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
1 siteCanada
Study dates
Oct 2014to Dec 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Male or female volunteer
  • A female volunteer must meet one of the following criteria:
  • Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first dosing, during the study and for at least 30 days after the last dosing or participant is of non-childbearing potential, i.e. surgically sterile or menopausal (at least 1 year without menses)
  • Age between 18 to 65 years
  • 35.00 kg/m2 ≥ Body Mass Index ≤ 18.50 kg/m2
  • Light-, non- or ex-smokers. A light smoker is smoking 2 cigarettes or less per day for at least 3 months before Day 1. An ex-smoker is someone who completely stopped smoking for at least 6 months before Day 1
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  • Barostat naive or no barostat experience in the year preceding screening
  • Clinical laboratory values within the laboratory's stated normal range; or without any clinical significance
  • Have no history of clinically significant diseases or evidence of clinically significant findings on physical exam and/or clinical laboratory tests
  • Have a normal anorectal area, confirmed by entry digital rectal exam (DRE) and
  • Signed dated informed consent form by subject

Who cannot join

  • Pregnant or lactating females
  • History of significant hypersensitivity to trimebutine, to sulfur-containing drugs or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
  • Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose undesired effects
  • Diagnosis of Inflammatory Bowel Disease or Irritable Bowel Syndrome
  • Criteria for functional bowel disorder (i.e. functional constipation, functional diarrhea and IBS) or abdominal pain, as reported by questionnaire
  • Known history of rectosigmoid disease
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  • Abnormal anorectal findings during entry DRE
  • History of abdominal surgery (except appendectomy or cholecystectomy)
  • History of gastrointestinal obstruction, any rectal or colon surgery
  • Known presence of piles or fissures, peri-anal pathology or any other rectal abnormalities
  • Female subjects with history of gynecological surgery (˂ 10 years prior to screening or 1 year for tubal ligation or hysterectomy)
  • Known history of, or risk factors for pelvic floor injury
  • History of significant gastrointestinal, liver or kidney disease, or surgery
  • Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
  • Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
  • Presence of out-of-range cardiac interval (PR < 110 msec, PR > 220 msec, QRS < 60 msec, QRS >119 msec and QTc > 450 msec for males and > 460 msec for females) on the screening elcetrocardiogram (ECG) or other clinically significant ECG abnormalities
  • Use of cysteine, methionine, and other sulfur-containing amino acid supplements in the previous 7 days before day 1 of this study;
  • Light-smoker who smokes cigar or is unable to refrain from smoking in the 7 days prior to the housing period and during the housing period of the study
  • Known presence of rare hereditary problems of galactose and/or lactose intolerance
  • Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (>3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
  • Any clinically significant illness in the previous 28 days before day 1 of this study
  • Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes and strong inducers of CYP enzymes in the previous 28 days before day 1 of this study;
  • Regular consumption of any supplement related to bowel movement in the previous 28 days before day 1 of this study
  • Positive urine screening of alcohol and/or drugs of abuse
  • Positive results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or anti-Hepatitis C Virus (HCV (C)) tests
  • Females pregnant according to a positive serum pregnancy test;
  • Subjects treated with any Investigational Product in the previous 28 days before Day 1 or who have already participated in this clinical study;
  • Prior donation of 50 mL or more of blood in the previous 28 days before Day 1
  • Prior total donation of 500 mL or more of blood in the previous 56 days before Day 1

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Algorithme Pharma Inc.

    Montreal, Quebec, H3P-3P1

Other trials in Canada

About this study

Official title: A Phase 1b Clinical Study on the Analgesic Effect of GIC-1001 and GIC-1002 on Visceral Pain Under Rectal Distension and Rectal Sensory Threshold Using the Barostat Method in Male and Female Healthy Volunteers.

This study evaluates colonic analgesia by comparing two novel formulations, GIC-1001 and GIC-1002 with placebo using a barostat distender. The healthy male and female volunteers randomized to one of 5 possible treatments will be exposed to rectal distension following a 3-day treatment TID. The barostat methodology is a well-established and validated way to assess visceral pain. Visceral pain will be evaluated during exposure to varying distender pressures using a visual analog scale.

Read the detailed description

The objectives of this single center, randomized, double-blinded, placebo-controlled Phase I clinical study include the evaluation of visceral pain intensity under rectal distension following the oral administration of either of two doses of GIC-1001 or of either of two doses of GIC-1002, equimolar to the first formulation, or of placebo in 90 healthy subjects.

The barostat intra-balloon pressure required to elicit pre-defined rectal sensory symptoms (i.e. first sensation, need to defecate, urgency to defecate and pain) will also be determined. Rectal sensory symptom ratings and rectal compliance under increased rectal distension will also be evaluated.

The contribution of hydrogen sulphide (H2S) to the colonic analgesic activity of GIC-1001 by comparison to that of GIC-1002 will be evaluated following steady state pharmacokinetic analysis. To further comprehend the non-linear, U shape dose response curve observed with GIC-1001 in a previous Phase II a trial.

Finally, the safety of GIC-1002 in healthy volunteers will also be evaluated.

Being tested
GIC-1001 375 mg TID, GIC-1001 500 mg TID, GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID), GIC-1002 460 mg (equimolar to GIC-1001 500 mg), Placebo
Keywords
rectal distension, rectal compliance, visceral pain, pain intensity, barostat, distender, VAS (Visual Analog Scale), rectal sensory threshold, analgesia, trimebutine, pain management, peripheral, colon cancer, H2S (hydrogen sulfide)
Medical subject headings
Pain, Neoplasms, Colonic Diseases, Visceral Pain, Agnosia, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GIC-1001 375 mg TIDDrug

    Also called trimebutine 3-thiocarbamoylbenzenesulfonate , TB-905-02

    GIC-1001 375 mg TID mid-dose, oral tablet, white-coated, to be taken with water

  • GIC-1001 500 mg TIDDrug

    Also called trimebutine 3-thiocarbamoylbenzenesulfonate , TB-905-02

    GIC-1001 500 mg TID high-dose, oral tablet, white-coated, to be taken with water

  • GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID)Drug

    Also called non-H2S releasing tosylate salt

    GIC-1002 345 mg TID mid-dose, oral tablet, white-coated, to be taken with water

  • GIC-1002 460 mg (equimolar to GIC-1001 500 mg)Drug

    Also called non-H2S releasing tosylate salt

    GIC-1002 460 mg TID high-dose, oral tablet, white-coated, to be taken with water

  • PlaceboOther

    Also called sugar -pill

    Placebo identical and matching active drugs GIC-1001 and GIC-1001

Study groups in NCT02276768
Study groupRoleWhat they receive
GIC-1001 mid-doseExperimentalGIC-1001 , 375 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
Receives: Drug: GIC-1001 375 mg TID
GIC-1001 high-doseExperimentalGIC-1001 , 500 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
Receives: Drug: GIC-1001 500 mg TID
GIC-1002 mid-doseActive comparatorGIC-1002 345 mg TID (equimolar to GIC-1001 375 mg) 345 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
Receives: Drug: GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID)
GIC-1002 high-doseActive comparatorGIC-1002 460 mg (equimolar to GIC-1001 500 mg) 460 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
Receives: Drug: GIC-1002 460 mg (equimolar to GIC-1001 500 mg)
Placebo matching GIC-1001 and GIC-1002Placebo comparatorPlacebo matching GIC-1001 doses Placebo matching GIC-1002 doses Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean visceral pain intensity score following dosing with GIC-1001 375 mg TID

    Mean visceral pain intensity score in millimeters (mm) on a 100-mm Visual Analog Scale (VAS) based on 7 measurements collected at increasing rectal distension pressures from 24 to 60 mmHg following the oral administration of the GIC-1001 375 mg TID x 3 days regimen, and comparing it to placebo.

    Measured: Stage IV, test lasts approximately 20 min.VAS scores collected every 2 minutes at a colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute.A 1-minute resting period follows between.

Secondary outcomes (13)

  1. Mean visceral pain intensity score following dosing with GIC-1001 500 mg TID

    Mean visceral pain intensity score in mm on a 100-mm VAS based on 7 measurements collected at increasing rectal distension pressures from 24 to 60 mmHg following the oral administration of the GIC-1001 500 mg TID x 3 days regimen, compared to placebo.

    Measured: Stage IV, test lasts approx. 20 min.VAS scores collected every 2 min. at colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute. A 1-minute resting period follows VAS scoring..

  2. Mean visceral pain intensity score following dosing with GIC-1002 345 mg TID and GIC-1002 460 mg TID

    Mean visceral pain intensity score in mm on a 100-mm VAS, based on 7 measurements collected at increasing rectal distension pressures from 24 to 60 mmHg following the oral administration of two doses of GIC-1002 (345 mg TID and 460 mg TID x 3 days regimen), compared to placebo.

    Measured: Stage IV, test lasts approx. 20 min.VAS scores collected every 2 min. at colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute. A 1-minute resting period follows VAS scoring.

  3. Barostat pressure required to elicit pre-defined rectal sensory symptoms

    Barostat intra-balloon pressure in mm Hg required to elicit pre-defined rectal sensory symptoms (i.e. first sensation, need to defecate, urgency to defecate and pain) following the oral administration of GIC-1001 or GIC 1002, respectively at two equimolar doses

    Measured: Stage III lasts about 15 min.VAS scores collected every 1 minute at increasing colorectal distension pressures: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and 60 mmHg. Each pressure is held for 1 minute for VAS score report. No resting period.

  4. Rectal sensory intensity score

    Rectal sensory intensity score (i.e. first sensation, need to defecate, urgency to defecate and pain) in mm on a 100-mm VAS following the oral administration of GIC-1001 or GIC-1002, respectively at two equimolar doses.

    Measured: Stage III lasts about 15 min.Intensity score recorded every minute at te same time as VAS for rectal sensory compliance...

  5. Rectal compliance under increasing rectal distension

    Rectal compliance in ml/mmHg under increased rectal distension following the oral administration of GIC-1001 or GIC-1002, respectively at two equimolar doses.

    Measured: Stage III lasts about 15 min. Overall rectal compliance is calculated over a 15-minute period with pressure increasing sequentially from 4 to 60 mmHg.

  6. Contributing hydrogen sulfide analgesia as evaluated by comparing mean visceral pain intensity score differences

    Contribution of H2S to GIC-1001 analgesic effects in terms of mean VAS scores differences between GIC-1001 and GIC-1002 at equimolar doses.

    Measured: Approx. 35 minutes, during total barostat testing period

  7. Steady state pharmacokinetic AUC (ng/ml/hour) for GIC-1001 and GIC-1002

    Steady State pharmacokinetics of GIC-1001 and GIC-1002 at the end of their proposed dosing regimens at pre-dosing times on Treatment Days 1, 2, 3 and on Day 4 of the barostat procedure then 8 hours post-dose .

    Measured: Pre-dose, 0, 24, 36, 72, 80 hours post dose

  8. Number of participants with adverse events

    Number of subjects reporting AEs during participation

    Measured: 5 days, from Treatment Day 1 until 24 hours post-barostat distension

  9. Number of adverse events

    Number of adverse events reported overall

    Measured: 5 days, from Treatment Day 1 until 24 hours post-barostat distension

  10. ECG measures

    Safety evaluation: Standard ECG measures

    Measured: At baseline and post-barostat Day 4

  11. Normality of physical exam

    Safety evaluation: Complete physical examination at both entry and exit

    Measured: At baseline and post-barostat Day 4

  12. Normality of Proctoscopic examination

    Safety evaluation: Evaluation of rectum

    Measured: On Day 4, prior and post barostat distension

  13. Standard laboratory measures (biochemistry, hematology, urinalysis)

    Safety evaluation: comparative assessment with baseline for all components

    Measured: At screening, pre-dosing (baseline) and post-barostat Day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02276768
Sponsor's protocol ID
GIC1.14.1.02
Other IDs
GCR-P7-403
Status last verified
Aug 2016
First submitted
20 Oct 2014
Last updated
10 Aug 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GIC-1001 375 mg TID, GIC-1001 500 mg TID and GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID) in people with Pain and Cancer, run by gicare Pharma Inc. at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean visceral pain intensity score following dosing with GIC-1001 375 mg TID (time frame: Stage IV, test lasts approximately 20 min.VAS scores collected every 2 minutes at a colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute.A 1-minute resting period follows between.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02276768.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2016.

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