| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| GASTRO-ESOPHAGEAL REFLUX DISEASE (GERD) |
|
| 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 | 10018203 |
| E.1.2 | Term | GERD |
|
| 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 understand the dose-response characteristics of PF-00885706 for efficacy in terms of symptomatic relief when used as add-on treatment to Esomeprazole 20mg (standard PPI treatment), in subjects with GERD who have inadequate relief with PPIs. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety of PF-00885706 in subjects with GERD in subjects who are poor responders to PPI treatment.
• To evaluate the population pharmacokinetics (POPPK) for PF-00885706 in a populationof subjects with GERD in order to support the development of a PKPD model.
• To validate a modified patient reported outcome (PRO) instrument [modified version ofthe Patient Assessment of Gastro-Intestinal SYMptoms {PAGI-SYM} instrument in both paper and electronic formats. |
|
| 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 indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Subjects with a diagnosis of GERD who fulfill the following criteria
• who have symptoms for at least six months prior to enrolment
• who are currently on daily treatment with a PPI and have been on such treatment for at least 3 months
• whose symptoms are persistent1, troublesome and that include heartburn and/or
regurgitation as their predominant symptoms despite treatment with a PPI
• who are seeking relief of persistent symptoms 1 persistent symptoms: Minimum of 4 days (in a week) with at least mild symptoms (i.e. symptom does not last long and is easily tolerated) or minimum of 2 days with moderate (i.e. symptom causes discomfort and interrupts usual activities including sleep) to severe symptoms (i.e. symptom causes great interference with usual activities [including sleep] and
may be incapacitating.
3. Male or female subject aged 18 to 65 years inclusive.
4. All female subjects must fulfill adequate contraception criteria
A negative serum or urine pregnancy test within 72 hours prior to start of study
medication for Women of Child Bearing Potential (WOCBP*). WOCBP include any
female who has experienced menarche and who has not undergone successful surgical sterilization or is not post-menopausal**. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products (intrauterine devices; barrier methods) to prevent pregnancy, who are practicing abstinence, or who have a partner that is sterile (e.g., vasectomy), should be considered to be of child bearing potential.
* Female subjects of non-childbearing potential must meet at least one of the following criteria:
**Postmenopausal females, defined as:
Females over the age of 60 years.
Females who are 45 to 60 years of age must be amenorrheic for at least 2 years PLUS have a serum FSH level within the laboratory’s reference range for postmenopausal women.
Females who had a hysterectomy and/or bilateral oophorectomy.
All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential.
Willingness to utilize an acceptable form of contraception***(e.g. hormonal contraception, intrauterine device, barrier method plus spermicide) for WOCBP from screening to at least a month after the study.
*** Acceptable contraceptive method for female subjects of childbearing potential include one of the following: Female subjects who wish to use nonhormonal contraception must have done so for at least 14 days prior to the first dose of study medication.
• Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs) at least 14 days prior to the first dose of study medication;
• Placement of a copper-containing intrauterine device (IUD);
• Condom with spermicidal foam/gel/film/cream/suppository;
• Male partner who has had a vasectomy for at least 4 months
5. Body Mass Index (BMI) of 18 to 40 kg/m2
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
1. Subjects not able or unwilling to provide informed consent and or to follow study
procedures or considered to be non compliant according to the investigator
2. Subjects with any of the following diseases/conditions
a. Zollinger-Ellison syndrome
b. Primary esophageal motility disorder, i.e. achalasia, scleroderma, primary
esophageal spasm or nutcracker esophagus.
c. Esophageal disorders such as strictures, upper GI endoscopic scoring of Los
Angeles grade D; dysphagia, Barrett’s esophagus,
d. Surgical or endoscopic treatment for GERD
e. History of esophageal, gastric or duodenal surgery, except for simple closure of
an ulcer OR gastric or duodenal ulcers.
f. Malabsorption or Inflammatory Bowel Disease
g. Irritable Bowel Syndrome
h. Large hiatus hernia
3. Subjects diagnosed with erosive esophagitis or alarm symptoms such as dysphagia; odynophagia; gastrointestinal bleeding or anemia; weight loss; and chest pain.
4. If female; pregnant, lactating or positive serum or urine pregnancy tests.
5. Subjects presenting with any of the following will not be included in the study:
• Cardiovascular
a. Subjects with a history of cardiovascular disease, e.g. ischemic heart disease,
arrhythmias, QT prolongation (> 450msec), myocardial infarction or stroke
b. Subjects with uncontrolled hypertension (BP > 140/90 mm of Hg) or having
symptomatic hypotension
c. Subjects with a significant history of symptomatic postural hypotension or
greater than a 20mmHg drop in systolic or 10 mmHg drop in diastolic blood
pressure on standing at screening
d. Subjects with a screening 12-lead ECG demonstrating any clinically
significant abnormality
• Renal impairment
• Alanine aminotransferase ≥2 times the ï€ upper limit of normal at screening (Visit 1) as defined by the central laboratory;
• Subjects with a history of malignancy who have not been in remission for at least 5
years at the time of the baseline visit.
Note for clarification: Subjects with basal and squamous cell carcinomas are eligible
for entry within the 5 year period provided they have been disease-free for 12 months at the time of entry, and they are followed up regularly by a dermatologist
• Uncontrolled diabetes mellitus (HbA1c > 7). Stable diabetes controlled by diet, oral
agents or insulin is acceptable
• History of ethanol abuse, substance abuse, or social situations that may affect
adherence to the study protocol
• Subjects with a positive Hepatitis B, Hepatitis C or HIV test.
6. Subjects who have received any investigational drug or device within 30 days of
screening, or who is scheduled to receive another investigational drug or device in the course of the study.
7. Subjects who are unable or unwilling to withdraw from prescribed proton pump
inhibitors and replace with standard study PPI treatment.
8. Subjects who are unable or unwilling to stop gastro-prokinetic or other drugs for the treatment of GERD for the duration of the study
9. Subjects who are unable to tolerate or are allergic to
a. Gaviscon™ or its excipients.
b. Esomeprazole treatment or their excipients.
10. Subjects who are taking, or have taken within 14 days of Visit 2, any
drugs that are known to be potent CYP3A4 inhibitors; potent CYP3A4 inducers and potent CYP2C19 inducers or inhibitors [see Appendix 10]
11. Subjects with factors that may interfere with efficacy assessment.
12. Subjects that have made a blood donation of approximately 500mL within 30
days prior to screening.
13. Subjects with any clinically significant laboratory abnormalities that may increase the risk associated with study participation or may interfere with the interpretation of the study results.
14. Subjects with a disease or condition affecting their well-being to the extent that may adversely influence the reliability of the patient reported outcomes measured in this study, e.g. changes in the quality of life recorded by patients with a painful condition will depend on the changes in that condition, not the effect of the study treatment. Other severe acute or chronic medical or psychiatric condition 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 subject inappropriate for entry into this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Complete resolution of heartburn and regurgitation [i.e. no more than one day with either mild heartburn or regurgitation over seven days prior to the assessment time point (Visit 6 and Visit 8)]. |
|
| 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 | Yes |
| 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 | 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 | 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
| |
| 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 | 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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