Clinical trial NCT00414856: Effects of AFQ056 and Baclofen on Meal-Induced Gastroesophageal Reflux
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroesophageal Reflux Disease
Keywords: GERD
gastroesophageal reflux disease
meal-induced gastroesophageal reflux events
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-12-22
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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 β2-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

Primary outcomes:
measure: Gastroesophageal reflux episodes as assessed by impedance measurements in the 4-hour period following a standardized high-fat meal in patients with GERD.
Secondary outcomes:
measure: Safety and tolerability of oral AFQ056 in GERD patients.
measure: Pharmacokinetics (PK) of two AFQ056 single oral doses in patients with GERD.
measure: Relationships between AFQ056 blood levels and/or how the body interacts with the medication and overall reflux incidence
measure: Validation of the reflux model used in this study using baclofen as positive control.
measure: Effects of AFQ056 on other impedance/pH parameters, including but not limited to the rate of reflux episodes at various time intervals
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Novartis Investigative site
city: Paris
country: France
facility: Novartis Investigative site
city: Nuernberg
country: Germany
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative site
Study officials:
affiliation: Investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References: