Efficacy and Safety of CB-01-11 200mg Tablets in Infectious Diarrhoea

• Sponsor: Cosmo Technologies Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03447821
• Collaborator: (none)
• Enrollment: 40
• Arms: 3
• Actual Duration (Months): 5

Study Details

Study Description

Brief Summary

To assess the safety and the preliminary efficacy data on the three doses of the new Cosmo Technologies oral rifamycin SV colon-release 200 mg tablets manufactured according to MMX technology (CB-01-11) in the treatment of infectious diarrhoea.

Condition or Disease	Intervention/Treatment	Phase
Infectious Diarrhoea	Drug: 400 mg Rifamycin SV dosage; Drug: 800 mg Rifamycin SV dosage; Drug: 1200 mg Rifamycin SV dosage	Phase 2

Detailed Description

To assess the safety and the preliminary efficacy data on the three doses of the new Cosmo Technologies oral rifamycin SV colon-release 200 mg tablets manufactured according to MMXTM technology (CB-01-11) in the treatment of infectious diarrhoea.

Primary end points to determine:

• The safety and preliminary efficacy data of the three doses of the new rifamycin SV formulation tested based upon the time elapsed from the ingestion of the 1st dose of study medication to the passage of the last unformed stool (TLUS), in compliance with the relevant guidelines

Secondary end-points to determine:

• The number of patients showing improvement in diarrhoea during a 24-h interval, i.e. >50 % reduction of bowel movements.

• The number of unformed stools passed per 24-h interval, after dosing.

• The number of patients who are declared to be "well". Wellness is defined as the patient having 48 hours with no unformed stools, a maximum of two soft stools and no clinical symptoms of infectious diarrhoea.

• The number of treatment failures. A treatment failure is defined as clinical deterioration or worsening of symptoms or illness continuing after 120 h following the first dose.

• The number and percentage of patients recovered from diarrhoea. Patients were considered to have recovered if fewer than three unformed stools were passed in the previous 24 hours and no symptom of enteric infection were present.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of CB-01-11 200mg Tablets in Infectious Diarrhoea. A Pilot, Dose Finding, Double-blind, Randomized, Multicentre Study
• Actual Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 400 mg Rifamycin SV dosage Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos.	Drug: 400 mg Rifamycin SV dosage
Active Comparator: 800 mg Rifamycin SV dosage Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos.	Drug: 800 mg Rifamycin SV dosage
Active Comparator: 1200 mg Rifamycin SV dosage Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos.	Drug: 1200 mg Rifamycin SV dosage

Outcome Measures

Primary Outcome Measures

1. Time to Last Unformed Stool (TLUS) [Up to 7 days]

   The safety and preliminary efficacy data of the three doses of the new rifamycin SV formulation tested based upon the time elapsed from the ingestion of the 1st dose of study medication to the passage of the last unformed stool (TLUS)

Secondary Outcome Measures

1. The Number of Patients Showing Improvement in Diarrhoea During a 48h Interval [48 hours]

   The evaluation of improvement in diarrhoea during a 48 hour interval is defined as a >50% reduction of bowel movements versus the baseline value

2. The Number of Unformed Stools Passed Per 24-h Interval [192 hours]

   The number of unformed stools passed per 24-h interval, after dosing

3. The Number of Patients Who Are Declared to be "Well" [48 hours]

   The patient having must meet all of the following criteria in order to be classified as "well": 48 hours with no unformed stools with a maximum of two soft stools and no clinical symptoms of infectious diarrhoea.

4. Number of Participants With Treatment Failure [120 hours]

   A treatment failure is defined as clinical deterioration or worsening of symptoms or illness continuing after 120 h following the first dose.

5. The Number of Patients Recovered From Diarrhoea [24 hours]

   Patients were considered to have recovered if fewer than three unformed stools were passed in the previous 24 hours and no symptom of enteric infection were present.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients had to meet all of the following inclusion criteria:

• Male and female patients aged 18-65 years inclusive on the date of screening.

• Patients with infectious diarrhoea (ID) in the active phase of no more than 72-h duration. Criteria for diagnosis of ID were: three or more unformed stools in the preceding 24 hours, and at least one symptom of enteric infection e.g. abdominal cramps/pain, tenesmus, urgency, an excess of gas/flatulence, nausea, vomiting.

• If female, and of child-bearing potential, use of an effective contraceptive method. (Oral contraceptives, injectable hormonal contraceptives, double-barrier method (condom/diaphragm with spermicide) and intra-uterine devices, according to the definition of Note 3 of ICH M3(M) Guideline. Females were considered not to be of child-bearing potential, if they were at least 12 months post-menopausal.

• Ability, in the investigator's opinion to comprehend the full nature and purpose of the study, including the possible risks and side effects, and willing to comply with the requirements of the study.

• Patients who have voluntarily signed and dated the informed consent document for screening and study specific procedures.

• Patients must be sufficiently literate to be able to complete a diary card.

Exclusion Criteria:

Patients had not to have had of any of the following:

• Females of child-bearing potential not using an effective contraceptive method.

• Pregnant or lactating females.

• Fever (defined as a body (axillary) temperature ≥ 38° C) present either at the screening visit or in the previous 24 hours.

• Visible presence of blood in the stool at baseline.

• Patients with any history or evidence on examination, of clinically significant gastrointestinal (in particular intestinal obstruction and severe intestinal ulcerative lesions), renal, hepatic, endocrine, respiratory, cardiovascular, dermatological or haematological disease, which in the opinion of the investigator could affect the interpretation of the efficacy and safety data.

• Patients with moderate or severe dehydration (see Appendix 2 of the protocol, for definitions of clinical symptoms).

• Prohibited previous and concomitant medication (see relevant section of the protocol).

• History of recent gastrointestinal malignancy (within 6 months).

• Allergy: presumptive or ascertained hypersensitivity to the study drug, history of anaphylaxis or allergic reactions in general.

• History of, or current misuse of alcohol, drugs or abuse of medication.

• Participation in another study with any investigational product within 3 months before screening.

• Patients who, in the opinion of the investigator, could be un-cooperative and/or non-compliant and should not therefore participate in the study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Cosmo Technologies Ltd

Investigators

• Principal Investigator: Manuel Mancera Reyes, HOSPITAL CENTRAL DE ORIENTE
• Principal Investigator: Can Polat Eyigün, Gülhane Military Medical Academy

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cosmo Technologies Ltd
• ClinicalTrials.gov Identifier: NCT03447821
• Other Study ID Numbers: CB-01-11/03
• First Posted: Feb 27, 2018
• Last Update Posted: Feb 18, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cosmo Technologies Ltd: Infectious diarrhoea; rifamycin SV; rifamycin SV MMX; MMX
• Additional relevant MeSH terms: Communicable Diseases; Infections; Dysentery; Diarrhea; Rifamycins; Rifamycin SV

Study Results

Participant Flow

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Period Title: Overall Study
STARTED	14	13	13
COMPLETED	13	12	12
NOT COMPLETED	1	1	1

Baseline Characteristics

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage	Total
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage	Total of all reporting groups
Overall Participants	13	12	12	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.5 (12.1)	37.3 (15.9)	41.9 (12.7)	39.6 (13.4)
Sex: Female, Male (Count of Participants)
Female	6 46.2%	8 66.7%	7 58.3%	21 56.8%
Male	7 53.8%	4 33.3%	5 41.7%	16 43.2%
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	165.2 (9.8)	160.8 (9.7)	159.1 (6.2)	161.8 (8.9)
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	72.3 (16.7)	72.9 (17)	70.3 (11.8)	71.8 (15)
Axillary Temperature (°C) (Degrees Celsius) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Degrees Celsius]	36.8 (0.5)	36.8 (0.4)	36.7 (0.4)	36.8 (0.4)

Outcome Measures

1. Primary Outcome

Title	Time to Last Unformed Stool (TLUS)
Description	The safety and preliminary efficacy data of the three doses of the new rifamycin SV formulation tested based upon the time elapsed from the ingestion of the 1st dose of study medication to the passage of the last unformed stool (TLUS)
Time Frame	Up to 7 days

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Measure Participants	13	12	12
Mean (Standard Deviation) [hours]	59.3 (12.1)	51.4 (12.3)	57.4 (13.1)

2. Secondary Outcome

Title	The Number of Patients Showing Improvement in Diarrhoea During a 48h Interval
Description	The evaluation of improvement in diarrhoea during a 48 hour interval is defined as a >50% reduction of bowel movements versus the baseline value
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Intent to treat

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Measure Participants	13	12	12
Showed improvement within 48 hrs	4 30.8%	9 75%	6 50%
Showed no improvement within 48 hrs	9 69.2%	3 25%	6 50%

3. Secondary Outcome

Title	The Number of Unformed Stools Passed Per 24-h Interval
Description	The number of unformed stools passed per 24-h interval, after dosing
Time Frame	192 hours

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Measure Participants	13	12	11
0-24 h	5.23 (2.74)	4.67 (3.17)	4.73 (3.41)
24-48 h	2.15 (1.95)	1.5 (1.57)	2.64 (2.66)
48-72 h	2.09 (1.64)	1.29 (1.6)	1.7 (1.95)
72-96 h	1.5 (1.29)	1.67 (2.08)	1.8 (2.05)
96-120 h	1.5 (0.71)	1.5 (2.12)	0.75 (0.96)
120-144 h	3 (0)	0.5 (0.71)	1 (0)
144-168 h	3 (0)	1 (0)	1 (0)
168-192 h	0 (0)	1 (0)	1 (0)

4. Secondary Outcome

Title	The Number of Patients Who Are Declared to be "Well"
Description	The patient having must meet all of the following criteria in order to be classified as "well": 48 hours with no unformed stools with a maximum of two soft stools and no clinical symptoms of infectious diarrhoea.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

intent to treat

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Measure Participants	13	12	11
Wellness Yes	13 100%	10 83.3%	2 16.7%
Wellness No	0 0%	2 16.7%	9 75%

5. Secondary Outcome

Title	Number of Participants With Treatment Failure
Description	A treatment failure is defined as clinical deterioration or worsening of symptoms or illness continuing after 120 h following the first dose.
Time Frame	120 hours

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Measure Participants	13	12	11
No	12 92.3%	10 83.3%	9 75%
Yes	1 7.7%	2 16.7%	2 16.7%

6. Secondary Outcome

Title	The Number of Patients Recovered From Diarrhoea
Description	Patients were considered to have recovered if fewer than three unformed stools were passed in the previous 24 hours and no symptom of enteric infection were present.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	400 mg Rifamycin SV Dosage	800 mg Rifamycin SV Dosage	1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
Measure Participants	13	12	11
No	1 7.7%	2 16.7%	2 16.7%
Yes	12 92.3%	10 83.3%	9 75%

Adverse Events

Arm/Group Title	400 mg Rifamycin SV Dosage		800 mg Rifamycin SV Dosage		1200 mg Rifamycin SV Dosage
Arm/Group Description	Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Four of the six daily tablet taken in this group were placebos. 400 mg Rifamycin SV dosage		Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. Two of the six daily tablet taken in this group were placebos. 800 mg Rifamycin SV dosage		Two enteric coated, modified release tablets, each containing 200 mg Rifamycin SV, taken three times daily. None of the six daily tablet taken in this group were placebos. 1200 mg Rifamycin SV dosage
All Cause Mortality
	400 mg Rifamycin SV Dosage		800 mg Rifamycin SV Dosage		1200 mg Rifamycin SV Dosage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	400 mg Rifamycin SV Dosage		800 mg Rifamycin SV Dosage		1200 mg Rifamycin SV Dosage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	400 mg Rifamycin SV Dosage		800 mg Rifamycin SV Dosage		1200 mg Rifamycin SV Dosage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/13 (30.8%)		3/12 (25%)		4/12 (33.3%)
Cardiac disorders
CARDIAC DISORDERS	0/13 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Gastrointestinal disorders
GASTROINTESTINAL DISORDERS	2/13 (15.4%)	2	3/12 (25%)	10	1/12 (8.3%)	2
General disorders
GENERAL DISORDERS	2/13 (15.4%)	2	0/12 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL	0/13 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
NERVOUS SYSTEM	0/13 (0%)	0	0/12 (0%)	0	3/12 (25%)	3
Psychiatric disorders
PSYCHIATRIC DISORDERS	1/13 (7.7%)	1	0/12 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
SKIN AND SUBCUTANEOUS	1/13 (7.7%)	1	0/12 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No disclosure was to take place without written authorisation from Cosmo Technologies Ltd, except to the extent necessary to obtain informed consent from potential volunteers.