| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Idiopathic Constipation |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063582 |
| E.1.2 | Term | Constipation chronic |
|
| 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 assess the efficacy of multiple dose levels of ATI-7505 in patients with chronic idiopathic constipation
|
|
| E.2.2 | Secondary objectives of the trial |
| To determine the safety and tolerability of ATI-7505 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria at Screening:
Patients are eligible to participate in the study if they:
a. are willing and able to provide written informed consent;
b. are male or female between 18 and 75 years of age, inclusive, at screening;
c. had constipation symptom onset at least 6 months ago;
d. have for the last 3 months prior to randomization, on average, fewer than 3 bowel
movements per week along with one or more of the following symptoms of constipation (Drossman 2006):
• Straining with ≥25% of defecations;
• Lumpy or hard stools with ≥25% of defecations;
• Sensation of incomplete evacuation ≥25% of defecations; or
• Sensation of anorectal obstruction/blockage for ≥25 % of defecations;
e. had a negative colonoscopy or air contrast barium enema (the latter in conjuction with flexible sigmoidoscopy) to exclude organic (mucosal) disease of the colon (along with the rectum and anus) within the past 5 years with unchanged constipation symptoms and no current suspicion of organic (mucosal) pathology. A negative result on computed tomographic (CT) colography, if already done within the past 5 years, with unchanged constipation symptoms and with no current suspicion of organic (mucosal) pathology is also acceptable.
Note: Run-in period may not start until at least 7 days after any of the colon imaging
procedures.
f. are female and are (as documented by verbally offered medical history):
• postmenopausal (at least 1 year without spontaneous menses), or
• surgically sterile (tubal ligation or hysterectomy), or
• using highly effective (ICH 1997) contraception (eg, oral, intramuscular, or implanted hormonal contraception [at least 3 months prior to enrollment], sexual partner with nonreversed vasectomy [with azoospermia in 2 tests], 2 independent barrier methods [ie, a combination of 2 of the following methods: condom, diaphragm, or properly applied spermicide], or intra-uterine device). Women who are using contraception will be required to have a pregnancy test (urine) at the Screening, Baseline/Day 1, Day 15, and Day 30 visits.
g. have had no changes in dose of selective serotonin reuptake inhibitor (SSRI) drugs (if they are taking them) in the 30 days prior to screening and are not planning such changes for the duration of the study;
h. have had no significant changes in diet, fiber intake, fluid intake, or physical activity in the 2 months prior to screening and are not planning such changes for the duration of the study;
i. are able to refrain from use of medications known to treat constipation or associated symptoms throughout the study except rescue medication as noted in protocol section 3.6.10.
Inclusion Criteria at Randomization
Patients are eligible for randomization to a treatment group in the study if they:
a. have, on average, fewer than 3 bowel movements per week during the 2-week run-in period;
b. have at least 1 bowel movement each week of the 2-week run-in period;
c. have had no significant changes in diet, fiber intake, fluid intake, or physical activity level during the 2-week run-in period;
d. have been at least 70% compliant during the 2-week run-in period with electronic patient reported outcome (ePRO) e-diary entries (at least 10 out of 14 e-diary entries); and
e. have not missed more than 3 consecutive days of e-diary entries. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from admission to the 2-week run-in period or randomization to a treatment group if they have/are:
a. a history of transabdominal surgery within the 6 months prior to screening;
b. presence or suspected presence of unstable coronary artery disease, organic gastrointestinal disease, or collagen vascular disease within the 6 months prior to screening;
c. any alarm symptoms including uninvestigated anemia, rectal bleeding, weight loss, or unresolved fever within the 6 months prior to screening;
d. taking prohibited medications specified in Section 3.3 within 30 days prior to screening or planning to take prohibited medications at any time during the study except laxatives used only as rescue medication consistent with protocol section 3.6.10;
e. participating in another drug or medical device study or use of any investigational drug within 30 days before dosing or planning to use prior to study completion;
f. at screening, a QT interval corrected for heart rate using Bazett’s correction formula (QTcB) >440 msec as calculated by the Investigator. The ECG core laboratory will also determine the QTcB and the QT interval corrected for heart rate using Fridericia’s correction formula (QTcF). If either QTcB or QTcF reported by the ECG core laboratory exceeds 440 msec, the patient will not be randomized;
g. at the baseline visit, a QTcB >440 msec as calculated by the Investigator;
h. a clinically significant abnormal 12-lead ECG with evidence of acute or recent myocardial infarction or ischemia, rhythm disturbance, or conduction abnormality other than first degree AV block;
i. a family history of sudden death at age <40 years;
j. a personal or family history of long QT syndrome;
k. evidence of current or recent alcohol or drug abuse within the 6 months prior to screening;
l. a serum potassium, magnesium, or calcium value outside the laboratory reference range at screening;
m. a serum aspartate transaminase (AST), alanine transaminase (ALT), or gamma glutamyl transferase (GGT) ≥3 times the upper limit of the normal laboratory reference range at screening or baseline, or a bilirubin value ≥2 times the upper limit of the normal laboratory reference range at screening;
n. a fasting blood glucose >2 times the upper limit of normal laboratory reference range at screening;
o. an abnormal thyroid stimulating hormone (TSH) value at screening, unless the free T4 value is normal;
Note: Stable doses of levothyroxine will be allowed during the study provided the doses have been stable (ie, have not changed) for at least 30 days prior to screening and are not expected to change for the duration of the study.
p. any laboratory value(s) outside the laboratory reference range at screening that are considered to be clinically significant by the Investigator;
q. more than a rare occurrence (more than 1 per month) of loose stools without the use of laxatives;
r. a history of or evidence of current laxative abuse;
s. experiencing continuous abdominal pain for more than 4 hours before bowel movements;
t. taking any herbal remedies, herbal laxatives, or laxative teas;
u. taking fiber supplementation or probiotics at dosages that have not been stable for at least the 2 months prior to screening or that are not expected to remain unchanged during the study;
Note: Fiber supplementation and probiotics at doses that have not changed in the 2 months prior to screening and are not expected to change during the study are allowed.
v. taken or planning to take protocol-specified rescue medication during the 48 hours
immediately preceding the first dose of study drug (evening of Day 1);
w. a known history or suspicion of autonomic dyssynergic defecation;
x. a positive pregnancy test or are nursing or planning a pregnancy during screening, run-in, active treatment, or the follow-up period; or
y. a history or presence, upon clinical evaluation, of any illness or condition that might impact the safety of study drug administration or evaluability of drug effect based on the Investigator’s discretion. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the total number of spontaneous bowel movements (SBM) during the first 7 days after randomization. For patients with 4 to 6 days of data recorded during the first week of treatment, the primary efficacy endpoint will be the imputed total number of SBMs over 7 days. For patients with less than 4 days of data recorded during the first week of treatment, the primary efficacy endpoint will be set to ‘missing’. This endpoint will be collected using a daily PRO assessment administered electronically via telephone. |
|
| 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 | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Yes |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| The study is considered terminated upon completion of all patient treatments and evaluations. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| 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 | 0 |
Print
