Effects of AFQ056 and Baclofen on Meal-Induced Gastroesophageal Reflux

Gastroesophageal Reflux Disease Clinical Trial

Official title:

A Multi-Center, Randomized, Double-Blind, Placebo- and Positive-Control, Double-Dummy, 3 Parallel Cohort, Two-Way Crossover Single Oral Dose Study in GERD (Gastro Esophageal Reflux Disease) Patients to Evaluate the Effects of AFQ056 and Baclofen (Positive Control) on the Incidence of Meal-Induced Gastro Esophageal Reflux Events

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00414856
• Other study ID #: CAFQ056A2108
• Status: Completed
• Phase: Phase 1
• First received: December 21, 2006
• Last updated: June 21, 2007
• Start date: August 2006

Study information

• Verified date: June 2007
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and tolerability of oral single dose applications of AFQ056 in GERD patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Male and female patients with GERD (18-60 years) with a history of moderate to severe reflux symptoms (heartburn or acid regurgitation more than 2 days/week, and/or night-time reflux, and/or after meal reflux) for = 3 months with:

• uncomplicated reflux-esophagitis of any degree as evidenced by esophagogastroduodenoscopy (EGD) within the last 12 months, OR (and) a pathological ambulatory 24-hours pH measurement within the last 12 months with pH < 4 for = 9% of the time.

• Females must be of no child bearing potential (postmenopausal women with no regular menstrual bleeding for at least 1 year or women who have been surgically sterilized at least 6 months prior). Menopause will be confirmed by a plasma FSH level of 37.0 – 185.0 mIU/mL. Surgical sterilization procedures must be supported with clinical documentation.

• Patients must be able to completely finish the high-fat breakfast within 15 minutes.

• Body mass index must be below 30. Patients must weigh at least 60 kg to participate in this study.

• Patients must be able to communicate well with the investigator, to understand and comply with the requirements of the study and to understand and sign the written informed consent.

Exclusion Criteria:

History of:

• Upper gastrointestinal (GI) surgery or radiation

• GI disorders other than GERD that may significantly affect the incidence and/or assessment of reflux episodes (GI motility disorders, connective tissue disease like scleroderma, Barrett’s esophagus, hiatal hernia > 3-4 cm, previous esophageal bleeding, esophageal varices, active gastric or duodenal ulcer disease, active esophagitis

• Delayed gastric emptying, or endoscopic indications for a delay in gastric emptying or gastric outlet obstruction.

• Neurologic/psychiatric disorders including a family history of epilepsy clinically significant cardiac disease

• Diabetes mellitus or other metabolic disorders including hyperlipidemia requiring treatment

• Any significant acute or chronic conditions except for following treated by the quoted drugs with a stable therapy for at least 4 weeks:

• Hypertension well-controlled with the following:

1. ACE inhibitors: benazepril, captopril, cilazapril, enalapril, fosinopril, imidapril, lisinopril, moexipril, perindopril tert-butylamine, quinapril, ramipril, spirapril, trandolapril, zofenopril, and/or

2. angiotensin II receptor antagonists: candesartan cilexetil, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, and/or

3. diuretics: amiloride, bendroflumethiazide, bumetanide, canrenoate de potassium, chlortalidone, cicletanine, clopamide, cyclothiazide, furosemide, hydrochlorothiazide, indapamide, methyclothiazide, piretanide, spironolactone, torasemide, triamterene, xipamide, and/or

4. calcium antagonists: bepridil, felodipine, isradipine, lercanidipine, manidipine, nimodipine, nitrendipine, amlodipine, nicardipine BUT NOT diltiazem, nifedipine, verapamil

• Well-compensated asthma with topical use of corticosteroids and/or ß2-mimetics

• Patients on thyroid hormone therapy with a normal TSH value.

• Nonsteroidal anti-inflammatory drugs including aspirin use in the week prior to treatment/impedance monitoring.

• Patients with body mass index = 30.

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• AFQ056

Locations

Country	Name	City	State
Belgium	Novartis Investigative site	Brussels
France	Novartis Investigative site	Paris
Germany	Novartis Investigative Site	Nuernberg
Switzerland	Novartis Investigative site	Bern

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gastroesophageal reflux episodes as assessed by impedance measurements in the 4-hour period following a standardized high-fat meal in patients with GERD.
Secondary	Safety and tolerability of oral AFQ056 in GERD patients.
Secondary	Pharmacokinetics (PK) of two AFQ056 single oral doses in patients with GERD.
Secondary	Relationships between AFQ056 blood levels and/or how the body interacts with the medication and overall reflux incidence
Secondary	Validation of the reflux model used in this study using baclofen as positive control.
Secondary	Effects of AFQ056 on other impedance/pH parameters, including but not limited to the rate of reflux episodes at various time intervals