Safety and Efficacy of Lansoprazole in Patients With Reflux Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01135368
First received: June 1, 2010
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to measure the safety, efficacy and quality of life of lansoprazole in patients with reflux disease over a five year period.


Condition Intervention Phase
Gastroesophageal Reflux
Drug: Lansoprazole
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Lansoprazole in Patients With Reflux Disease. An Open, Single Arm, Long-term Study

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in Reflux Disease Symptom - Heartburn [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Heartburn symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

  • Change From Baseline in Reflux Disease Symptoms - Acid Regurgitation [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Acid regurgitation symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

  • Change From Baseline in Reflux Disease Symptom - Difficulty Swallowing [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Difficulty swallowing symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

  • Change From Baseline in Reflux Disease Symptom - Pain in Upper Abdomen [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Pain in the upper abdomen symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

  • Change From Baseline in Reflux Disease Symptom - Nausea & Vomiting [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Nausea and vomiting symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

  • Change From Baseline in Reflux Disease Symptom - Cough & Sore Throat [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Cough and sore throat symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

  • Change From Baseline in Endoscopic Healing of Erosive Reflux Disease as Assessed by Endoscopy [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Los Angeles Classification is used to grade the extension of changes in the oesophagus induced by reflux disease (Grade 0: normal aspect of mucosa; Grade A: ≥1 mucosal breaks no longer than 5 mm; Grade B: ≥1 mucosal breaks >5 mm long; Grade C: mucosal breaks extending between tops of two or more mucosal folds but are <75% of the circumference; Grade D: mucosal breaks ≥75% of the circumference). Healed defined as anything less than Grade A criteria. The shift table below summarizes the individual transitions in Los Angeles classification between Baseline (table columns) and Week 8 (table rows).


Secondary Outcome Measures:
  • Change From Baseline in Enterochromaffin-like Cell Hyperplasia [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    Enterochromaffin-like (ECL) cells were evaluated and classified by histopathological examinations as Normal, Simple (diffuse) hyperplasia, or Linear, chain producing hyperplasia.

    The shift table below summarizes the individual transitions in ECL-cell classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows) for all patients.


  • Change From Baseline in Antrum Atrophy [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Atrophy was assessed by histopathological examination of cells biopsied from the antrum and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in atrophy classification (mild, moderate, severe or none) between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Corpus Atrophy [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Atrophy was assessed by histopathological examination of cells biopsied from the corpus and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in atrophy classification (mild, moderate, severe or none) between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Average Antrum Chronic Inflammation Score [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Chronic inflammation of the antrum was assessed by histopathology and graded according to the Sydney classification: 0 = None; 1 = mild; 2 = moderate; 3 = Severe

  • Change From Baseline in Corpus Chronic Inflammation Score [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Chronic inflammation of the corpus was assessed by histopathology and graded according to the Sydney classification: 0 = None; 1 = mild; 2 = moderate; 3 = Severe.

  • Change From Baseline in Antrum Intestinal Metaplasia [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Intestinal metaplasia was assessed by biopsy and histopathological examination of the antrum and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in intestinal metaplasia classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Corpus Intestinal Metaplasia [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Intestinal metaplasia was assessed by biopsy and histopathological examination of the corpus and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in intestinal metaplasia classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Blood Analysis - Testosterone [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The change between testosterone measured at year 5 in males including final visit and Testosterone measured at baseline.

  • Change From Baseline in Blood Analysis - Luteinizing Hormone [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The change between luteinizing hormone measured at year 5 in males including final visit and luteinizing hormone measured at baseline.

  • Change From Baseline in Blood Analysis - Follicle Stimulating Hormone [ Time Frame: Baseline and Year 5. ] [ Designated as safety issue: Yes ]
    The change between follicle stimulating hormone (FSH) measured at year 5 in males including final visit and follicle stimulating hormone measured at baseline.

  • Ophthalmologic Examination - Visual Acuity [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Visual Acuity was measured using the Snellen eye chart at a distance of 6 meters. Acuity is expressed as a ratio of the test distance (6 M) / the distance the average eye can see the letters on a certain line of the eye chart. Visual acuity of 1 is normal; an individual with acuity of 0.5 could only recognize an object at half the distance compared to an individual with normal acuity.

  • Change From Baseline in Ophthalmologic Examination - Adaptation Without Glare [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    Adaptation is the ability of the eye to adjust to various levels of darkness and light. Normal and pathological status of adaptation without glare was defined as follows:

    • Normal status: Contrast between 1:0.05 and 1:23.5.
    • Pathological status: Contrast = 0 or contrast > 1:23.5.

    The shift table below summarizes the individual transitions in the classification of adaptation without glare between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


  • Change From Baseline in Ophthalmologic Examination - Adaptation With Glare [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    Adaptation is the ability of the eye to adjust to various levels of darkness and light. Normal and pathological status of adaptation with glare was defined as follows:

    • Normal status: Contrast between 1:0.05 and 1:23.5.
    • Pathological status: Contrast = 0 or contrast > 1:23.5.

    The shift table below summarizes the individual transitions in the classification of adaptation with glare between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


  • Change From Baseline in Ophthalmologic Examination - Accommodation [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Accommodation is the adjustment of the focal length of the eye lens to keep an object in focus on the retina as its distance from the eye varies, and is measured in diopters: Diopters = 1/(focal length).

  • Change From Baseline in Ophthalmologic Examination - Color Vision [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    Color vision was assessed by an Ophthalmologist and classified as normal or pathological. Pathological findings include abnormal color vision tests, color blindness and anomalous quotient. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in color vision classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Cornea Assessment of Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The cornea of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, corneal degeneration, opacity, scars or deposits. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in corneal classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Cornea Assessment of Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The cornea of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, corneal degeneration, opacity, scars or deposits. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in corneal classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Lens Assessment of Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    The lens of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5.

    Pathological classification includes abnormal findings such as cataracts, lenticular opacities, vacuoles or pseudophakia. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in lens classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


  • Change From Baseline in Ophthalmologic Examination - Lens Assessment of Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    The lens of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5.

    Pathological classification includes abnormal findings such as cataracts, lenticular opacities, vacuoles or pseudophakia. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in lens classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


  • Change From Baseline in Ophthalmologic Examination - Vitreous Body Assessment of Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    The vitreous body of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5.

    Pathological classification includes abnormal findings such as myodesopsia, vitreous opacities, degeneration, detachment or prolapse. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in vitreous body classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


  • Change From Baseline in Ophthalmologic Examination - Vitreous Body Assessment of Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]

    The vitreous body of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5.

    Pathological classification includes abnormal findings such as myodesopsia, vitreous opacities, degeneration, detachment or prolapse. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in vitreous body classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


  • Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Aspect of the Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The retinal aspect of the right eye (such as color anomalies) was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as deep red ocular fundus, fundus myopicus, retinal disorders, exudates or pigmentation. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal aspect classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Aspect of the Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The retinal aspect of the left eye (such as color anomalies) was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as deep red ocular fundus, fundus myopicus, retinal disorders, exudates or pigmentation. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal aspect classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Optic Nerve and Papilla of the Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The optic nerve and papilla of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as optic nerve cupping, optic nerve cup/disc ratio, or glaucomatous optic disc atrophy. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in optic nerve/papilla classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Optic Nerve and Papilla of the Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The optic nerve and papilla of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as optic nerve cupping, optic nerve cup/disc ratio, or glaucomatous optic disc atrophy. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in optic nerve/papilla classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Blood Vessels of the Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The retinal blood vessels of the right eye were assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as retinal vascular disorder, retinopathy, and retinal hemorrhage. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal blood vessel classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Blood Vessels of the Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The retinal blood vessels of the left eye were assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as retinal vascular disorder, retinopathy, and retinal hemorrhage. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal blood vessel classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Macula Lutea of the Right Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The macula lutea of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as maculopathy, retinal pigmentation, macular degeneration, diabetic retinopathy, retinal hemorrhage or aneurysm. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in macula lutea classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

  • Change From Baseline in Ophthalmologic Examination - Assessment of Macula Lutea of the Left Eye [ Time Frame: Baseline and Year 5 ] [ Designated as safety issue: Yes ]
    The macula lutea of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as maculopathy, retinal pigmentation, macular degeneration, diabetic retinopathy, retinal hemorrhage or aneurysm. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in macula lutea classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).


Enrollment: 506
Study Start Date: June 2002
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lansoprazole

Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.

Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.

Drug: Lansoprazole
Lansoprazole capsules
Other Names:
  • Prevacid
  • Helicid
  • Zoton
  • Inhibitol
  • Agopton
  • AG-1749

Detailed Description:

Lansoprazole is currently approved in Germany for the treatment of erosive reflux esophagitis and active duodenal and gastric ulcer disease, and for long-term treatment including maintenance of healed reflux esophagitis and duodenal ulcer disease and treatment of pathological hypersecretory conditions such as Zollinger-Ellison syndrome.

This study was conducted to evaluate the safety, efficacy and quality of life of patients receiving up to five years of treatment with lansoprazole.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Had Gastro Esophageal Reflux disease with or without oesophagitis.
  • Had a history of heartburn at least for 5 days per week during the past 6 months or was receiving long-term treatment with a proton pump inhibitor and during two weeks (without proton pump inhibitor treatment) prior to enrolment.

Exclusion Criteria:

  • History of surgery of stomach or oesophagus.
  • Gastric ulcer (can be included after healing of gastric ulcer).
  • Duodenal ulcer (can be included after healing of duodenal ulcer).
  • Bleeding (melena, hematemesis).
  • Severe concomitant disease (cancer, cardiovascular, renal, hepatic diseases).
  • Barrett oesophagus with dysplasia.
  • Complicated esophagitis (oesophageal strictures or ulcers).
  • Treatment with proton pump inhibitor or Histamine receptor 2 (H2)antagonists within the previous two weeks.
  • Pregnancy, wish to become pregnant, breast feeding.
  • Treatment with non steroidal anti-inflammatory drugs, treatment with acetylsalicylic acid (aspirin) > 100 mg/day.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01135368     History of Changes
Other Study ID Numbers: AGO K019, U1111-1115-1139
Study First Received: June 1, 2010
Results First Received: July 25, 2012
Last Updated: July 25, 2012
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by Takeda:
GERD
Gastroesophageal Reflux Disease
Drug Therapy

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Lansoprazole
Dexlansoprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014