E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
A form of inflammatory bowel disease |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
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 |
To evaluate the long-term safety and tolerability and potential efficacy of APD334 in patients with ulcerative colitis who have completed the APD334-03 study. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of APD334 on achieving and maintaining clinical response and/or remission in patients with ulcerative colitis after 52 weeks of treatment. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document
2. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and is deemed an appropriate candidate for participation in this long-term extension study
3. Eligible female patients must be:
a. non-pregnant, evidenced by a negative urine dipstick pregnancy test at Week 12 of study APD334-003
b. non-lactating
c. sexually abstinent (if this is the preferred and usual lifestyle of the individual. Periodic abstinence [calendar, symptothermal, post-ovulation methods], withdrawal [coitus interruptus], and lactational amenorrhoea method are not acceptable methods of contraception), surgically sterile, postmenopausal, or agree to continue to use an accepted method of birth control during and for at least 30 days after last study medication administration. Acceptable methods of birth control are:
- hormonal contraceptives (patients should be consistently taking the hormonal contraceptive for at least 3 months [90 days] prior to screening);
- double barrier method (condom and occlusive cap [diaphragm or cervical cap] with spermicide);
- an intrauterine device;
- surgical sterility for at least 6 months prior to screening for tubal ligation performed laparoscopically, hysterectomy and/or bilateral oophorectomy; and/or postmenopausal (defined as at least 2 years without menses).
Contraceptive measures such as Plan B (used after unprotected sex) are not acceptable methods of contraception for this study.
4. Eligible male patients must:
- Agree to use the double-barrier method (condom and occlusive cap [diaphragm or cervical cap] with spermicide) when sexually active with a female partner who is pregnant, breastfeeding, or not using an acceptable method of birth control, during the study and for 30 days after last study medication administration
5. Eligible male and female patients must agree not to participate in a conception process (i.e. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for 30 days after the last dose of study drug
6. Completion of the APD334-003 study. |
|
E.4 | Principal exclusion criteria |
1. Patients who were withdrawn from study drug treatment due to any AE or SAE, or patients who did not complete the APD334-003 study
2. Female patients who wish to become pregnant
3. Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is long-term safety. The safety of APD334 will be monitored throughout the study with safety endpoints being as follows:
- Treatment-emergent adverse events (AEs) up to 30 days
following discontinuation of the study drug.
- Treatment-emergent serious adverse events (SAEs) up to 30 days following discontinuation of the study drug. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout study up to 30 days after discontinuation of study drug |
|
E.5.2 | Secondary end point(s) |
In responders who transitioned from study APD334-003 to
APD334-005:
- The proportion of patients who maintain clinical response
[defined as a decrease in 3-component Mayo Clinic score of ≥ 2
points and at least 30% with either a decrease of rectal bleeding
of ≥ 1 or rectal bleeding score of 0 or 1] at Week 52 compared to
APD334-003 baseline
- The proportion of patients who achieve clinical remission
[defined as individual subscores of the 3-component Mayo
Clinic score as follows: an endoscopy score (using flexible
proctosigmoidoscopy) of 0 or 1, a rectal bleeding score of 0, and
a stool frequency score of 0 or 1 with a decrease of ≥ 1 point
from baseline at Week 52 compared to APD334-003 baseline |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Bulgaria |
Canada |
Germany |
Hungary |
Latvia |
Lithuania |
Poland |
Romania |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
United States |
|
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
|
Last visit of the last subject |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 15 |