Affects of Once-daily Oral Administration of TZP-102 on the Treatment of Symptoms Associated With Diabetic Gastroparesis

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Evaluation of the Efficacy and Safety of Once-Daily Administrations of TZP-102 for the Treatment of Symptoms Associated With Diabetic Gastroparesis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01452815
• Other study ID #: TZP-102-CL-G003
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2011
• Last updated: April 24, 2013
• Start date: September 2011
• Est. completion date: November 2012

Study information

• Verified date: August 2012
• Source: Tranzyme, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsBelgium: Federal Agency for Medicinal Products and Health ProductsDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyGermany: Paul-Ehrlich-InstitutNorway: Norwegian Medicines AgencySweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the safety and effectiveness of two dosage levels (10mg and 20mg) of TZP-102 compared to placebo (capsule that looks like the study drug but contains no active drug), administered once-daily for 12 weeks, in diabetic subjects with symptoms associated with gastroparesis.

Description:

Considered subjects will be screened to determine eligibility for entry into the study. The Screening Visit must take place at least 14 days, but not more than 21 days, before the planned date of study entry (randomization and administration of the first dose of study drug on Study Day 1). The baseline evaluation of gastric emptying must be scheduled at least 7 days (in the U.S.) and 10 days (in Europe) before the Day 1 Visit. Subjects will answer questions relating to their gastroparesis symptoms in an electronic diary (like a palm pilot) beginning on the first day of the screening period.

Eligible subjects will be randomized to receive placebo or one of two dosages of TZP-102 (10mg or 20mg) once daily for 12 weeks. After randomization and administration of the first dose of study drug on Study Day 1 (the Study Entry Visit), subsequent visits to the clinic will be scheduled every two weeks during the 12-week Treatment period and 4-week Follow-Up Period.

All visits will be conducted on an outpatient basis. Visits for a given subject throughout the study should be scheduled to start at approximately the same time, in the morning. Subjects will be instructed to take their daily dose of study drug each morning (when not attending a study visit), at least 30 minutes before breakfast. Subjects will be instructed to not take study drug on the morning of each treatment period visit and to bring study drug supplies with them to the clinic; study drug will be administered in the clinic after all scheduled assessments/procedures (after all pre-dose assessments at each of the Day 1 and Week 12 Visits) are completed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 18 to 80 years of age, inclusive

• Type 1 or type 2 diabetes mellitus

• History of symptoms of gastroparesis for at least 3 months leading up to the Screening Visit

• Gastric half-emptying time >82 minutes, demonstrated by the Gastric Emptying Breath Test performed at the Screening Visit OR documented delayed gastric emptying within the previous 24 months

• Mild to moderate severity of gastroparesis symptoms during the screening period

• Body Mass Index (BMI) < 45.0 at the Screening Visit

• Glycosylated hemoglobin (HbA1c) level < 11.0% at the Screening Visit

• Upper gastrointestinal obstruction ruled out by endoscopy or barium scan

• Concomitant medications must be stable for at least 2 weeks leading up to the Baseline Visit and must be maintained during the study.

• Females of child-bearing potential must have a negative serum pregnancy test and use (and agree to continue to use throughout the study) an acceptable form of contraception.

Exclusion Criteria:

• Persistent daily vomiting

• Gastrectomy, bariatric surgery, fundoplication or vagotomy/pyloroplasty

• Has had or plans to have endoscopic pyloric injections of botulinum toxin within 6 months prior to the Screening Visit or during the study.

• NG, PEG or PEJ feeding tube within 2 weeks prior to the Screening Visit

• Required in-patient hospitalization for treatment of gastroparesis within 2 weeks prior to the Screening Visit

• Required parenteral nutrition for treatment of gastroparesis within 2 months prior to the Screening Visit

• Active gastric pacemaker within 3 months prior to the Screening Visit

• Participated in an investigational study within 30 days prior to the Screening Visit

• Chronic severe diarrhea

• Diabetic ketoacidosis that required inpatient hospitalization within 30 days prior to the Screening Visit

• History of any eating disorder within 2 years prior to the Screening Visit

• Chronic obstructive pulmonary disease (COPD) or chronic asthma

• Chronic smoker that is unable or unwilling to abstain from smoking during the two visits that the gastric emptying breath test will be performed

• History of risk factors for Torsades de Pointes

• Corrected QT interval calculated using Fredericia's formula >= 500 msec, recorded and confirmed on any of the three ECG assessments performed during the screening period

• Bradycardia or hypotension assessed as clinically-significant by the investigator

• Requires treatment with concomitant medication that is a substrate of Cytochrome P450 isoenzyme 3A4 and known to have a clinically recognized risk for Torsades de Pointes

• History of acute myocardial infarction, unstable angina or a transient (cerebral) ischemic attack within 12 months prior to the Screening Visit

• History of severe depression, psychiatric disorder or cognitive impairment

• History of alcohol or drug abuse or dependency within 2 years prior to the Screening Visit

• Taking opiates for abdominal pain

• Known history of Hepatitis B or C or HIV infection

• Requires dialysis or elevated creatinine at the Screening Visit

• Abnormal liver function tests at the Screening Visit

• Uncontrolled hypo- or hyperthyroidism

• Adrenal insufficiency

• Active malignancy other than basal cell or squamous cell carcinoma of the skin

• Pregnant or breast-feeding

• Allergies to components of the breath test meal or severe lactose intolerance

• Any other medical condition or social circumstance that, in the investigator's opinion, makes it inappropriate for the patient to participate in this clinical trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Gastroparesis

Intervention

Drug:
• Placebo
Two #2 oval shaped,opaque-white, hard gelatin shell capsules containing inactive ingredients taken orally once daily for 12 weeks.
• 10mg TZP-102
One 10mg #2 oval shaped, opaque-white, hard gelatin shell capsule containing active ingredients and one placebo capsule each taken orally once daily for 12 Weeks
• 20mg TZP-102
Two 10mg #2 oval shaped, opaque-white, hard gelatin shell capsules containing active ingredients

Locations

Country	Name	City	State
Belgium	Tranzyme Investigational Site	Brugge
Belgium	Tranzyme Investigational Site	Bruxelles
Belgium	Tranzyme Investigational Site	Gent
Denmark	Tranzyme Investigational Site	Aarhus
Denmark	Tranzyme Investigational Site	Gentofte
Denmark	Tranzyme Investigational Site	Odense
Finland	Tranzyme Investigational Site	Porvoo
Finland	Tranzyme Investigational Site	Tampere
Germany	Tranzyme Investigational Site	Essen
Germany	Tranzyme Investigational Site	Mainz
Germany	Tranzyme Investigational Site	Stuttgart
Norway	Tranzyme Investigational Site	Bergen
Poland	Tranzyme Investigational Site	Bialystok
Poland	Tranzyme Investigational Site	Bydgoszcz
Poland	Tranzyme Investigational Site	Kielce
Poland	Tranzyme Investigational Site	Krakow
Poland	Tranzyme Investigational Site	Lodz
Poland	Tranzyme Investigational Site	Olsztyn
Poland	Tranzyme Investigational Site	Warszawa
Sweden	Tranzyme Investigational Site	Stockholm
Sweden	Tranzyme Investigational Site	Uppsala
United States	Tranzyme Investigational Site	Anderson	Indiana
United States	Tranzyme Investigational Site	Boston	Massachusetts
United States	Tranzyme Investigational Site	El Paso	Texas
United States	Tranzyme Investigational Site	Fayetteville	North Carolina
United States	Tranzyme Investigational Site	Hialeah	Florida
United States	Tranzyme Investigational Site	Houston	Texas
United States	Tranzyme Investigational Site	Huntsville	Alabama
United States	Tranzyme Investigational Site	Inverness	Florida
United States	Tranzyme Investigational Site	Jackson	Tennessee
United States	Tranzyme Investigational Site	Jacksonville	Florida
United States	Tranzyme Investigational Site	Jonesboro	Arkansas
United States	Tranzyme Investigational Site	Kansas City	Kansas
United States	Tranzyme Investigational Site	Little Rock	Arkansas
United States	Tranzyme Investigational Site	Long Beach	California
United States	Tranzyme Investigational Site	Mexico	Missouri
United States	Tranzyme Investigational Site	Miami	Florida
United States	Tranzyme Investigational Site	Miami	Florida
United States	Tranzyme Investigational Site	Monroe	Louisiana
United States	Tranzyme Investigational Site	New Smyrna Beach	Florida
United States	Tranzyme Investigational Site	Oak Lawn	Illinois
United States	Tranzyme Investigational Site	Oklahoma City	Oklahoma
United States	Tranzyme Investigational Site	Philadelphia	Pennsylvania
United States	Tranzyme Investigational Site	Port Orange	Florida
United States	Tranzyme Investigational Site	Portland	Oregon
United States	Tranzyme Investigational Site	Raleigh	North Carolina
United States	Tranzyme Investigational Site	Salisbury	North Carolina
United States	Tranzyme Investigational Site	Stanford	California
United States	Tranzyme Investigational Site	Tacoma	Washington
United States	Tranzyme Investigational Site	Tucson	Arizona
United States	Tranzyme Investigational Site	Ventura	California
United States	Tranzyme Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Tranzyme, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  Finland,  Germany,  Norway,  Poland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in symptoms associated with diabetic gastroparesis		12 Weeks	No
Secondary	Change from baseline on health-related quality of life		12 Weeks	No
Secondary	Adverse Events (AEs)		12 Weeks	Yes
Secondary	Cardiovascular Parameters (blood pressure, heart rate, 12-Lead ECG)		12 Weeks	Yes
Secondary	Clinical Chemistry and Hematology Parameters		12 Weeks	Yes