A Phase IIa, Multi-Centre, Double-blind, Randomised, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of K(D)PT after Multiple Ascending Doses in Patients with Active Mild to Moderate Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2010-023494-19-SE
• Date of registration: 27/12/2010
• Prospective Registration: Yes
• Primary sponsor: Dr. August Wolff GmbH & Co. KG Arzneimittel
• Public title: A Phase IIa, Multi-Centre, Double-blind, Randomised, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of K(D)PT after Multiple Ascending Doses in Patients with Active Mild to Moderate Ulcerative Colitis
• Scientific title: A Phase IIa, Multi-Centre, Double-blind, Randomised, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of K(D)PT after Multiple Ascending Doses in Patients with Active Mild to Moderate Ulcerative Colitis
• Date of first enrolment: 10/02/2011
• Target sample size: 12
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023494-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of signed, dated and written informed consent prior to any study specific procedures.
2. Adult males/females aged 18 to 70 years inclusive.
3. Have a body mass index (BMI) =18 and =35 kg/m2.
4. Females must have a negative pregnancy test at screening and on admission to the unit.
5. Females of child-bearing potential must agree to use medically acceptable methods of contraception.
6. Females of non-child-bearing potential should fulfil either of the following criteria at screening:
- post menopausal defined as amenorrhoea for greater than 1 year following cessation of all exogenous hormonal treatments and with follicle stimulating hormone (FSH) and luteinising hormone (LH) in the laboratory defined post-menopausal range
OR
- documentation of irreversible surgical sterilisation by bilateral oophorectomy, bilateral salpingectomy and hysterectomy but not tubal ligation.
7. Male patients must avoid fathering.
8. Mild to moderate active ulcerative colitis confirmed by a CAI between 4 and 9.
9. No pre-treatment of active ulcerative colitis except for:
- stable dose of mesalazine, sulfasalazine or olsalazine in the usual maintenance dose for >4 weeks before time of consent (the medication may be optimised [and administered via the oral or rectal route] by a referring gastroenterologist just before the patient enters the study, i.e within 5 days of first dose of IMP but not after first dose)
OR
- stable dose of azathioprine or mercaptopurine in the usual maintenance dose for >4 weeks before time of consent (the medication may be optimised [and administered via the oral or rectal route] by a referring gastroenterologist just before the patient enters the study, i.e within 5 days of first dose of IMP but not after first dose).

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:
1. Previous participation in any clinical study with K(D)PT.
2. Morbus Crohn.
3. Any clinically relevant abnormal findings in physical examination or clinical laboratory tests (clinical chemistry, haematology, urinalysis, coagulation) at screening, vital signs (supine blood pressure and heart rate) or ECG pre-dose Day 1, which, in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study.
4. 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 influence the results or the patient’s ability to participate in the study.
5. History of bleeding disturbance or thrombotic disorder.
6. History of or current alcohol or drug abuse, as judged by the Investigator.
7. Participation in another investigational drug study within 3 months before first administration of IMP or participation in a method development study (no drug) 1 month prior to first administration of IMP (Note: participation is identified as the completion of a treatment-related visit).
8. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks prior to the first administration of IMP.
9. Donation of blood within 3 months, or donation of plasma within 14 days, prior to first administration of IMP.
10. Other pre-treatment of ulcerative colitis than mesalazine, sulfasalazine, olsalazine, azathioprine or mercaptopurine.
11. Proctosigmoiditis (less than 25 cm).
12. Use of antibiotics within 6 weeks prior to first administration of IMP.
13. Previous anti-TNF therapy.
14. Marcumarisation or moderate to severe grade coagulation defects as judged by the Investigator.
15. Haemoglobin (Hb) value below 100 g/L (females) or 110 g/L (males).
16. QTcF >450 ms or <350 ms or QT >500 ms or other ECG abnormality making interpretation more difficult as judged by the Investigator.
17. A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the Investigator.
18. Significant hypersensitivity or allergy, as judged by the Investigator.
19. Allergy against methylparaben or propylparaben.
20. Positive results on screening tests for hepatitis B and/or C and/or human immunodeficiency virus (HIV).
21. Positive result on screening tests for drugs of abuse at screening.
22. Positive screen for alcohol breath test at screening/admission to the unit.
23. Positive stool result for any of the enteric pathogens: Clostridium, Salmonella, Shigella, Campilobacter or Yersinia.
24. Involvement in the planning and conduct of the study.
25. Planned in-patient surgery, dental procedure or hospitalisation during the study.
26. Patients who in the opinion of the Investigator should not participate in the study.
27. Patients who are unwilling or unable to participate in the study.



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

Health Condition(s) or Problem(s) studied

Ulcerative colitis
MedDRA version: 12.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis

Intervention(s)

Product Name: Lysine-D-Proline-Threonine
Product Code: K(D)PT
Pharmaceutical Form: Powder for oral solution
Pharmaceutical form of the placebo: Oral liquid
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The main objective of the trial is to assess the safety and tolerability of K(D)PT after administration of multiple ascending doses in patients with active mild to moderate ulcerative colitis.

Primary end point(s): Safety evaluation include vital signs, ECG parameters, physical examination, safety laboratory tests and adverse events.

If data allows, the following PK parameters will be determined for K(D)PT and its metabolite DKP on Day 1:
Cmax, tmax, AUC(0-24), MR

If data allows, the above PK parameters will be determined for K(D)PT and its metabolite DKP also on Day 6. In addition, the following PK parameters will be determined Day 6:
tlast, AUC(0-t), t½, CL/F, Vz/F, Rac, MRT, Ae, CLR

Steady-state will be evaluated by graphical presentation of pre-dose plasma concentrations (Ctrough) Days 2 (i.e. the Day 1 24 hour sample), 6 and 7 (i.e. the Day 6 24 hour sample) versus time (day) plots.

The following PK diagnostic parameters from Day 6 will be calculated and listed but not summarised by descriptive statistics in tables:
• The time interval of the log-linear regression to determine t½ (lambda lower/upper)
• Number of data points included in the log-linear regression analysis (a minimum of 3 points will be used).
• Regression coefficient (Rsq), if Rsq is less than 0.80, then t½, Vz/F and MRT will be flagged for low precision.
Additional PK parameters may be determined if considered relevant.

Safety Review Committee and Data Safety Monitoring Board will evaluate available safety, tolerability and PK data between each cohort.

Secondary Objective: To determine the pharmacokinetics (PK) of K(D)PT after administration of multiple ascending doses in patients with active mild to moderate ulcerative colitis.

Secondary ID(s)

KPT3-07/2010

Ethics review

Status: Approved
Approval date: 12/01/2011
Contact: