Clinical trial to evaluate the efficacy and safety of K(D)PT in patients with mild to moderate ulcerative colitis

• Register: EUCTR
• Last refreshed on: 17 June 2013
• Main ID: EUCTR2011-002462-20-HU
• Date of registration: 22/09/2011
• Prospective Registration: Yes
• Primary sponsor: Dr August Wolff GmbH & Co KG Arzneimittel
• Public title: Clinical trial to evaluate the efficacy and safety of K(D)PT in patients with mild to moderate ulcerative colitis
• Scientific title: Randomised, double-blind, placebo-controlled prospective clinical trial to evaluate the efficacy and safety of K(D)PT in patients with mild to moderate ulcerative colitis - K(D)PT in ulcerative colitis: proof of concept study
• Date of first enrolment: 07/12/2011
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002462-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Czech Republic, Germany, Hungary, Italy, Poland

Contacts

• Name: Clinical trial information
• Affiliation: Dr August Wolff GmbH & Co KG Arzneimittel

• Name: Clinical trial information
• Affiliation: Dr August Wolff GmbH & Co KG Arzneimittel

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide written informed consent, i.e. they must be willing and able to comply with the study procedures.
2. Adult males or females, aged 18 to 70 years (inclusive).
3. Females of childbearing potential must have a negative urine pregnancy test at screening and must agree to use adequate contraception (e.g. oral, depot or implanted hormonal contraception, intrauterine device, surgical sterilisation or partner vasectomy, or doble barrier method) from screening visit until at least 4 weeks after last dose of study medication (Week 12). A double barrier method means condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, cream of suppository.A female condom and a male condom should not be used together as friction between the two can result in either product failing.
4. Females of non-child bearing potential should be postmenopausal for >1 year or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy).
5. Male patients must agree to use adequate contraception (e.g. vasectomy or adequate partner contraception).
6. Body mass index (BMI) =19 and =30 kg/m2.
7. Mild to moderately active UC proven by endoscopy and criteria according to European Crohn's and Colitis Organisation (ECCO) guidelines and defined as a CAI of 6 to 12.
8. Pre-treatment of active ulcerative colitis with any of the following:
- a stable dose of oral mesalazine, sulphasalazine or olsalazine for >4 weeks (oral), and/or
- a stable dose of azathioprine or 6-mercaptopurin for >3 months, and/or
- a stable dose of oral corticosteroids of =20 mg oral prednisolone or equivalent for >2 weeks before baseline (Visit 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 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1. Pregnant, planning to become pregnant during the study, or breast feeding females.
2. Previous participation in any clinical study with K(D)PT.
3. Crohn’s disease.
4. Treatment-naive.
5. Infectious diarrhoea within the screening period (up to 14 days prior the randomization visit (Visit 2)), after randomization or during the treatment period.
6. Indeterminate colitis.
7. Significantly impaired liver, renal, pulmonary or cardiovascular function.
8. Use of systemic or topical gastrointestinal antibiotics within 4 weeks before or during the treatment period(day 1).
9.Use of E. coli Nissle within 4 weeks before or during the treatment period.
10. Previous use of cyclosporine, anti-TNF therapy (e.g. infliximab) or tacrolimus at any time.
11. Any rectal therapy four weeks before or during the treatment period.
12. Use of corticosteroids >20 mg oral prednisolone or equivalent.
13. Use of methotrexate within 3 months before or during the treatment period.
14. Use of anti-diarrhoeal drugs within 2 weeks before or during the treatment period.
15. Effective anti-coagulation therapy (e.g. Marcumar) or severe grade coagulation defects.
16. Any clinically relevant abnormal findings at screening, vital signs or ECG which, in the opinion of the investigator, may put the patient at risk because of his or her participation in the study. Patients must have undergone colonoscopy for dysplasia screening according to local guidelines before randomization.
17. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or could influence the results, or the patient’s ability to participate in the study.
18. History of or current alcohol or drug abuse, as judged by the investigator.
19. Participation in another investigational drug study within 3 months before first administration of study medication.
20. Donation of blood within 3 months, or donation of plasma within 2 weeks, before the first administration of study medication. Planned donation of blood, plasma or sperm at any time during the study (from the start of screening until follow up visit).
21. Proctitis (=5 cm).
22. QTcF >450 ms or <350 ms or QT >500 ms or other relevant ECG abnormality as judged by the investigator.
23. History of pathological skin condition or melanoma within the previous 5 years.
24. Known intolerance to methylparaben or propylparaben.
25. Known intolerance to any other excipient of the investigational medicinal product (IMP).
26. Positive history of hepatitis B and/or C and/or history of human immunodeficiency virus (HIV).
27. Planned surgery or hospitalisation during the study.
28. Patients who, in the opinion of the investigator, should not participate in the study.
29. Patients unable to understand informed consent.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Acute mild to moderate ulcerative colitis.
MedDRA version: 14.1 Level: LLT Classification code 10066678 Term: Acute ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: KdPT
Product Code: 20 mg
Pharmaceutical Form: Powder for oral solution
Current Sponsor code: K(D)PT Acetate
Other descriptive name: L-Lysyl-D-Prolyl-L-Threonine Acetate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Powder for oral solution
Route of administration of the placebo: Oral use

Product Name: KdPT
Product Code: 50 mg
Pharmaceutical Form: Powder for oral solution
Current Sponsor code: K(D)PT Acetate
Other descriptive name: L-Lysyl-D-Prolyl-L-Threonine Acetate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Powder for oral solution
Route of administration of the placebo: Oral use

Product Name: KdPT
Product Code: 100 mg
Pharmaceutical Form: Powder for oral solution
Current Sponsor code: K(D)PT Acetate
Other descriptive name: L-Lysyl-D-Prolyl-L-Threonine Acetate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Powder for oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: This is a proof of concept placebo-controlled study to determine the efficacy and safety of 3 dose groups of K(D)PT in patients with acute mild to moderate ulcerative colitis.
The primary objective is to determine the time to response to K(D)PT, defined as the time from Day 0 to the earliest treatment visit at which a sustained improvement in CAI of =50% is determined (CAI scored according to Rachmilewitz, 1989). The improvement in CAI must be =50% at week 8 (Visit 7) irrespective of any interim decline, for the improvement to be classified as sustained.

Primary end point(s): The primary endpoint is the time to sustained response to study medication, where response is defined as an improvement in CAI of =50% from Day 0 (CAI scored according to Rachmilewitz, 1989). The improvement in CAI must be =50% at week 8 (visit 7), irrespective of any interim decline, for the improvement to be classified as sustained.

Secondary Objective: To determine:
• remission at Weeks 4, 8 and 12, defined as CAI =3
• response at Weeks 4, 8 and 12, defined as an improvement in CAI of =50% from Day 0
• improvement in CAI during the (total) treatment period defined as the area under the curve of CAI values from Day 1 until Week 8.
• response at Week 8, defined as a decrease from baseline in Disease Activity Index (DAI) of 30% or more
• response at Week 8, defined as a change from baseline in endoscopy index (EI) of >1.5
• endoscopic remission, defined as flexible proctosigmoidoscopy score of 0 to 1 at Week 8.
• the improvement in faecal calprotectin concentration from baseline to Weeks 4, 8, and 12.
• the improvement in C-reactive protein (CRP) from baseline to Weeks 4, 8, and 12.
• the improvement in the score for Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline to Weeks 8 and 12.
• the incidence of adverse events (AEs) throughout the study.

Timepoint(s) of evaluation of this end point: Week 2, week 4, week 6, week 8 and week 12

Secondary Outcome(s)

Secondary end point(s): • Frequency of remission, defined as CAI =3 (CAI scored according to Rachmilewitz, 1989), at Weeks 4, 8 and 12.
• Response to study medication at Weeks 4, 8 and 12, where response is defined as an improvement in CAI of =50% (CAI scored according to Rachmilewitz, 1989).
• Area under the curve for the change from baseline in CAI scores during the (total) treatment period from Day 1 until Week 8
• Frequency of response rates at Week 8 with response defined as decrease from baseline in DAI of 30% or more
• Frequency of response rates at Week 8 with response defined as change from baseline in EI of >1.5
• Frequency of patients with endoscopic remission
• Change from baseline to Weeks 4, 8, and 12 in faecal calprotectin concentrations.
• Change from baseline to Weeks 4, 8, and 12 in CRP concentrations.
• Change from baseline to Week 8 and 12 in IBDQ scores.

Timepoint(s) of evaluation of this end point: Varies between day 1 to week 12.

Secondary ID(s)

2011-002462-20-DE

KPT4-01/2011

Source(s) of Monetary Support

Dr August Wolff GmbH & Co KG Arzneimittel