E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
To determine the pharmacokinetics (PK) of K(D)PT after administration of multiple ascending doses in patients with active mild to moderate ulcerative colitis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as last patient last visit (LPLV), which is the timepoint after which no patient will be exposured to study related activities (follow-up). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |