Clinical trial NCT01452815: Affects of Once-daily Oral Administration of TZP-102 on the Treatment of Symptoms Associated With Diabetic Gastroparesis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Keywords: diabetic gastroparesis
delayed gastric emptying
gastroparesis
diabetes mellitus, Type 1
diabetes mellitus, Type 2
Lead sponsor: Tranzyme, Inc.
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in symptoms associated with diabetic gastroparesis
timeFrame: 12 Weeks
Secondary outcomes:
measure: Change from baseline on health-related quality of life
timeFrame: 12 Weeks
measure: Adverse Events (AEs)
timeFrame: 12 Weeks
measure: Cardiovascular Parameters (blood pressure, heart rate, 12-Lead ECG)
timeFrame: 12 Weeks
measure: Clinical Chemistry and Hematology Parameters
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Tranzyme Investigational Site
state: Alabama
city: Tucson
country: United States
facility: Tranzyme Investigational Site
state: Arizona
city: Jonesboro
country: United States
facility: Tranzyme Investigational Site
state: Arkansas
city: Little Rock
country: United States
facility: Tranzyme Investigational Site
state: Arkansas
city: Long Beach
country: United States
facility: Tranzyme Investigational Site
state: California
city: Stanford
country: United States
facility: Tranzyme Investigational Site
state: California
city: Ventura
country: United States
facility: Tranzyme Investigational Site
state: California
city: Hialeah
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: Inverness
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: Miami
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: Miami
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: New Smyrna Beach
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: Port Orange
country: United States
facility: Tranzyme Investigational Site
state: Florida
city: Oak Lawn
country: United States
facility: Tranzyme Investigational Site
state: Illinois
city: Anderson
country: United States
facility: Tranzyme Investigational Site
state: Indiana
city: Kansas City
country: United States
facility: Tranzyme Investigational Site
state: Kansas
city: Monroe
country: United States
facility: Tranzyme Investigational Site
state: Louisiana
city: Boston
country: United States
facility: Tranzyme Investigational Site
state: Massachusetts
city: Mexico
country: United States
facility: Tranzyme Investigational Site
state: Missouri
city: Fayetteville
country: United States
facility: Tranzyme Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Tranzyme Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: Tranzyme Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Tranzyme Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Tranzyme Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: Tranzyme Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: Tranzyme Investigational Site
state: Pennsylvania
city: Jackson
country: United States
facility: Tranzyme Investigational Site
state: Tennessee
city: El Paso
country: United States
facility: Tranzyme Investigational Site
state: Texas
city: Houston
country: United States
facility: Tranzyme Investigational Site
state: Texas
city: Tacoma
country: United States
facility: Tranzyme Investigational Site
state: Washington
city: Brugge
country: Belgium
facility: Tranzyme Investigational Site
city: Bruxelles
country: Belgium
facility: Tranzyme Investigational Site
city: Gent
country: Belgium
facility: Tranzyme Investigational Site
city: Aarhus
country: Denmark
facility: Tranzyme Investigational Site
city: Gentofte
country: Denmark
facility: Tranzyme Investigational Site
city: Odense
country: Denmark
facility: Tranzyme Investigational Site
city: Porvoo
country: Finland
facility: Tranzyme Investigational Site
city: Tampere
country: Finland
facility: Tranzyme Investigational Site
city: Essen
country: Germany
facility: Tranzyme Investigational Site
city: Mainz
country: Germany
facility: Tranzyme Investigational Site
city: Stuttgart
country: Germany
facility: Tranzyme Investigational Site
city: Bergen
country: Norway
facility: Tranzyme Investigational Site
city: Bialystok
country: Poland
facility: Tranzyme Investigational Site
city: Bydgoszcz
country: Poland
facility: Tranzyme Investigational Site
city: Kielce
country: Poland
facility: Tranzyme Investigational Site
city: Krakow
country: Poland
facility: Tranzyme Investigational Site
city: Lodz
country: Poland
facility: Tranzyme Investigational Site
city: Olsztyn
country: Poland
facility: Tranzyme Investigational Site
city: Warszawa
country: Poland
facility: Tranzyme Investigational Site
city: Stockholm
country: Sweden
facility: Tranzyme Investigational Site
city: Uppsala
country: Sweden
facility: Tranzyme Investigational Site
Study officials:
affiliation: Tranzyme Pharma
name: Connie Cosentino
role: STUDY_DIRECTOR
References:
citation: McCallum RW, Lembo A, Esfandyari T, Bhandari BR, Ejskjaer N, Cosentino C, Helton N, Mondou E, Quinn J, Rousseau F; TZP-102 Phase 2b Study Group. Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil. 2013 Nov;25(11):e705-17. doi: 10.1111/nmo.12184. Epub 2013 Jul 15.