Chemotherapy-induced diarrhoea MedDRA version: 9.1 Level: LLT Classification code 10012745 Term: Diarrhoea NOS
Conditions
Interventions
Product Name: Transdermal Mecamylamine
Product Code: AGI004
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: MECAMYLAMINE
CAS Number: 60402
Current Sponsor code: AGI 004
Other descriptive
Sponsors
AGI Therapeutics Research Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria - All patients must: 1) Be aged 18 years and older. 2) Have had diarrhoea of NCI grade 1or 2 with no significant complicating factors. 3) Have a life expectancy of > 3 months. 4) Have at least two further cycles of chemotherapy planned. 5) Provide signed written informed consent. 6) Must be able to make entries into paper-based diary on a daily basis. 7) WHO performance status 0 – 2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A potential participant will be excluded from the study if they are patients with: 1) Acute or chronic diarrhoea or ileostomy / colostomy. 2) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 (Patients must have recovered from any major surgery). 3) Near future planned radiotherapy to abdomen or pelvis for underlying disease (prior completed radiotherapy treatment allowed). 4) Uncontrolled CNS metastases. 5) Any skin condition, which may, in the opinion of the Investigator, impair the use of transdermal patches. 6) Irritable Bowel Disease, inflammatory bowel disease or other conditions that could be an underlying cause of diarrhoea. 7) Have active gastric or duodenal ulcer, bowel obstruction or diverticulitis. 8) Lactose intolerance, whose lactose intolerance symptoms are not completely or substantially relieved solely by abstaining from dairy products. (Patients with lactose intolerance on a lactose free diet who qualify otherwise, may be enrolled). 9) Coeliac disease (diagnosed by serology or duodenal biopsy). 10) Unexplained fever or weight loss of at least 10 pounds during the last 6 months, or any clinically significant symptoms, e.g. patients with rectal bleeding or a recent change in pattern of bowel habits (unless they have had a pre-screening colonoscopy to eliminate any other diseases of the GI tract that might explain the symptoms). 11) Abnormal laboratory tests, positive stool cultures or abnormal proctoscopy / abdominal ultrasound which requires further investigation. 12) History of intestinal obstruction, stricture, toxic megacolon, GI perforation, faecal impaction. 13) History of laxative abuse as determined by the Investigator. 14) History of GI bleeding based on clinical judgment that would interfere with the subject’s safety or with the efficacy assessments of the study, or if the subject has had GI bleeding on two or more occasions within six weeks prior to study enrolment (with the exception of blood from haemorrhoids). 15) Presence of pathogenic parasites, ova, bacteria or any occult blood in stools which in the opinion of the Investigator may be responsible for GI symptoms (if measured within one month of Visit 1). 16) Glaucoma, organic pyloric stenosis, uraemia. 17) Pregnancy or lactation. Women of childbearing potential must maintain effective contraception 18) Evidence of formal psychiatric illness, apart from depression (not major), which is controlled by antidepressants 19) Past or present alcohol or drug abuse, which in the opinion of the Investigator may interfere with the conduct of the study. 20) History of myocardial infarction (MI) within 3 months of screening or New York Heart Association (NYHA) class III or IV congestive heart failure (CHF). 21) History of cerebrovascular accident (CVA) or transient ischaemic attack (TIA) within 3 months of screening, 22) Systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHG at screening. 23) Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg at screening, which in the opinion of the Investigator may interfere with the conduct of the study. 24) Clinically abnormal ECG at randomisation visit, in the opinion of the Investigator 25) Coronary insufficiency. 26) Participation in any other clinical trial within the last month. 27) Has shown previous intolerance/sensitivity to the study medication. 28) Impairment of haematological, hepatic or other end-organ function, which in the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective will be to determine the efficacy of transdermal mecamylamine in the control of chemotherapy-induced diarrhoea. ;Secondary Objective: 1) Secondary objectives relating to other aspects of patient’s diarrhoea will be recorded in a patient diary (Bristol Stool Scale).These will include the total number of episodes of diarrhoea, mean duration of episodes of diarrhoea, total duration of episodes of diarrhoea, percentage of days on treatment experiencing loose stools (scores >5) and the association between stool consistency and study treatments. 2) Secondary objectives relating to symptoms associated with patient’s diarrhoea will be recorded, on a 4-point scale, in a patient diary along with the use of rescue medication in relief of each symptom, and specifically the number of loperamide and codeine phosphate tablets used daily. These symptoms will include nausea, vomiting, constipation, diarrhoea, abdominal pain and abdominal cramping. ;Primary end point(s): There will be two primary endpoints: 1) The proportions of patients who experience diarrhoea receiving one of two active dose levels per cycle. Diarrhoea will be defined a) according to NCI CTCAE version 3 and b) derived from the Bristol Stool Scale diary as the number of bowel movements being > 4 on any given day29. Similarly, responders will be defined a) as patients who do not have diarrhoea according to NCI grades and b) as having < 4 bowel movements on all study days of each cycle 29 according to patients Bristol Stool Scale diary. Partial responders will be defined as those with a reduction of one NCI grade on treatment. Responders and partial responders will be sub-categorised into temporal periods of the day of chemotherapy and from day 1 to end of cycle. 2) The mean number of bowel movements per day receiving one of two active dose levels per cycle. Again, patients will be sub-categorised into temporal periods of the day of chemotherapy and from day 1 to end of cycl | — |
Countries
United Kingdom
Outcome results
None listed