Severe diarrhoea Digestive System
Conditions
Interventions
Run-In Period:
Intervention: Loperamide.
Dose: 4 mg (2 tablets) starting dose, followed by 2 mg (1 tablet) after each loose stool.
Route: Oral capsules.
Duration: 12-36 hours.
Control Arm:
Interventi
Sponsors
Pharmanovia (Atnahs Pharma UK Ltd)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 07/03/2025: 1. Aged 18 years or above. 2. Chemotherapy- and/or radiotherapy-induced severe diarrhoea, defined by adapted Common Terminology Criteria for Adverse Events (CTCAE) v5.07 grading, as below: 2.1. Grade 2 with at least 1 of the following additional risk factors leading to the investigator classifying the diarrhoea as severe: 2.1.1. Older age, defined as 65 or over 2.1.2. Female 2.1.3. Eastern Cooperative Oncology Group (ECOG) >2 2.1.4. Associated bowel pathology such as lactose intolerance 2.1.5. Presence of tumour in bowel 2.1.6. Treatment with agents such as irinotecan or capecitabine 2.1.7. Weekly chemotherapy schedule 2.1.8. Infusional chemotherapy 2.1.9. Prior history of cancer treatment induced diarrhoea 2.1.10. Concomitant abdominal-pelvic radiation and chemotherapy or 2.2. Grade 3 or 2.3. Grade 4 3. At the point of randomisation to be currently experiencing an episode of severe diarrhoea where the use of loperamide has not given sufficient effect. 4. Able and willing to give consent to the trial prior to participation. 5. Have access to a smartphone, tablet or laptop with internet access. 6. Female participants of child bearing potential(1) must be willing to ensure that they or their partner use effective contraception(2) or be willing to abstain(3) from sex during the trial. 7. Male participants must use a condom whilst receiving trial treatment and for 3 months after receiving the last IMP dose when having sexual intercourse with a woman of childbearing potential or a pregnant or breastfeeding partner. In addition, female partners of male participants should be advised to also use highly effective contraception if they are of childbearing potential. 8. In the Investigator’s opinion, is able and willing to comply with all trial requirements. 9. Willing to allow his or her General Practitioner, if appropriate, to be notified of participation in the trial. (1) Females/women of child bearing potential are defined as: Fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, menopausal status will be confirmed in line with NICE guidance. (2) Highly effective methods have typical-use failure rates of less than 1% and include sterilisation, long-acting reversible contraceptive (LARC) methods (intrauterine devices) and combined or progesterone-only hormonal contraception associated with inhibition of ovulation. (3) Sexual abstinence is defined as: Refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Note: Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Previous participant inclusion criteria: 1. Aged 18 years or above 2. Chemotherapy- and/or radiotherapy-induced sev
Exclusion criteria
Exclusion criteria: 1. Current treatment with immunotherapy or targeted therapies 2. Severe renal or hepatic impairment, defined as eGFR less than 40 ml/min/1.73 m² and LFTs above 2 x the ULN (1) 3. Confirmed or suspected pancreatitis 4. At risk of paralytic ileus 5. Known history of: 5.1. Opiate dependency 5.2. Alcohol use disorder 5.3. Glaucoma 5.4. Delirium tremens 5.5. Severe head trauma 5.6. Chronic obstructive pulmonary disease 5.7. Acute asthma 5.8. Severe respiratory depression with hypoxia and/or hypercapnia 5.9. Heart failure secondary to lung disease 6. Participants who have a stoma 7. Participants at high risk of falls 8. Participants with Clostridium difficile (C. diff) infection (2) 9. Participants who are intolerant to loperamide (3) 10. Any other significant disease or disorder which, in the opinion of the Investigator, may put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial 11. Female participants of child bearing potential who are pregnant, lactating or planning pregnancy during the course of the trial. Female participants of child bearing potential who have not already had a negative pregnancy test prior to commencing chemotherapy or radiotherapy should complete a pregnancy test to confirm they are not pregnant 12. Surgical operation within the past 7 days or scheduled within a week after randomisation 13. Co-enrolment in another clinical trial of investigational medicinal products (CTIMP) 14. Hypersensitivity to the active substances or to the excipients 15. Ongoing use of the following medications: disulfiram, metronidazole, morphine agonists/antagonists (buprenorphine, nalbuphine, nalmefene, naltrexone, pentazocine) and opioids (e.g. alfentanil, butorphanol, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, oxycodone, oxymorphone, remifentanil, sufentanil, tapentadol, tramadol). Participants who are expected to require any of these medications during the trial are also excluded (4) (1) LFTs include ALT and AST. Kidney and liver function results from blood tests conducted as SoC within the previous 48 hours are permitted (2) C. diff results from stool sample tests conducted as SoC within the previous 48 hours are permitted (3) Unable to tolerate the adverse effects of loperamide (4) Investigators should refer to the SmPCs for a full list of warnings and precautions, and should exclude participants at their discretion if concerned about cautionary interactions of the IMPs and concomitant medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants achieving a 50% reduction in stool frequency recorded above their normal baseline is measured using clinical assessment of diarrhoea at baseline until the end of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to resolution is measured using clinical assessment at baseline and day 21 post-randomisation 2. Improvement of quality of life score is measured using EQ-5D-5L at baseline, 48 hours, and day 7 post-randomisation 3. Improvement of gastrointestinal symptoms is measured using PROMIS-GI at baseline and day 7 post-randomisation 4. Healthcare resource utilisation is measured using medical records and an HCRU questionnaire at baseline, end of treatment, and days 7, 14, and 21 post-randomisation 5. Recurrence rate prior to the next chemotherapy and/or radiotherapy cycle is measured using clinical assessment of diarrhoea at baseline, days 1-5 on treatment, and days 7, 14, and 21 post-randomisation 6. Safety and tolerability are measured using adverse event reporting from the start of the run-in period until day 21 post-randomisation | — |
Countries
England, United Kingdom
Contacts
Public ContactAlexandra Robbins
Outcome results
None listed