|Principal Investigator: John Fang|
|Keywords: Gastroparesis , Tradipitant||Department: Gastroenterology|
|IRB Number: 00129133|
|Recruitment Status: Recruiting|
The underlying pathophysiology of gastroparesis is complex and remains largely unknown.
Prokinetic therapy has been the traditional mainstay of gastroparesis treatments, but studies continue to demonstrate a lack of correlation between reduction in gastric emptying delays and relief of gastroparesis symptoms.
Two case reports have documented the efficacy of open-label NK-1 antagonist therapy in severe, refractory gastroparesis cases. Thus, NK-1 receptor antagonists, like tradipitant, are promising potential therapeutics for treating nausea associated with gastroparesis.
To evaluate the efficacy of tradipitant relative to placebo in change from baseline to Day 28 in the weekly average of daily nausea severity scores.
To evaluate the efficacy of tradipitant relative to placebo in change from baseline in individual nausea severity scores reported daily at Week 12 (Day 84).
To evaluate the efficacy of tradipitant relative to placebo in change from baseline in number of days at “0” nausea score.
To evaluate the efficacy of tradipitant relative to placebo in change from baseline of other individual symptoms associated with gastroparesis.
To evaluate the efficacy of tradipitant relative to placebo in change from baseline of the overall symptom burden associated with gastroparesis.
To evaluate the efficacy of tradipitant relative to placebo in change from baseline of global improvement and quality of life measures.
To explore the safety and tolerability of multiple oral doses of tradipitant.
To identify genetic markers that correlate with response to tradipitant treatment.
To identify genetic markers that correlate with adverse events that may occur upon treatment with tradipitant.
To identify genetic markers that are associated with gastroparesis and/or gastroparesis symptoms and diseases associated with NK-1 receptors.
To identify genetic markers that are associated in the metabolism, distribution, and/or excretion of tradipitant and its metabolites.
To evaluate the effect tradipitant has on gastric emptying relative to placebo in change from baseline of gastric emptying rate.
Male and female subjects aged 18 – 70 years (inclusive);
Diagnosed with gastroparesis;
a. Demonstrated delayed gastric emptying of a solid meal via either scintigraphy, gastric breath test, or wireless motility capsule within 10 years of screening. If solid meal is not tolerated, a liquid meal may be used instead to demonstrate delayed gastric emptying via scintigraphy
b. Presence of nausea symptom for at least 6 months prior to screening
Patient’s gastroparesis symptoms persist despite diet and/or life-style modifications;
Body Mass Index (BMI) of ≥18 and < 40 kg/m2 (BMI = weight (kg)/ [height (m)]2);
Subjects must agree to the following study restrictions:
Males of procreative capacity (not surgically sterile) will use an acceptable method of contraception from randomization through 1 month following the last dose of study medication. Examples of acceptable contraception for males include abstinence, use of a barrier method, or sterilized or post-menopausal partner;
Females of child-bearing potential (not surgically sterile or post-menopausal, defined as 12 months without menses) will use an acceptable method of contraception from 1 month prior to randomization (or screening, if earlier) through 1 month following the last dose of study medication. Examples of acceptable methods of contraception for females include abstinence, double barrier method, IUD, hormonal contraception, or sterilized partner;
Ability and acceptance to provide written informed consent;
Willing to participate in the pharmacogenomics sample collection;
Willing and able to comply with all study requirements and restrictions, including but not limited to:
c. Daily symptom diary completion,
Strict control of blood glucose (T1DM and T2DM patients);
9. Willing to not participate in any other interventional trial for the duration of their participation.
NOTE: ADDITIONAL CRITERIA ARE CONFIDENTIAL AND SHOULD NOT BE SHARED WITH SUBJECTS, POTENTIAL SUBJECTS, OR ANYONE OUTSIDE OF THE IMMEDIATE STUDY TEAM.
Additional Inclusion Criteria for Group 1/Evaluation Phase:
10. Diagnosed with idiopathic or diabetic gastroparesis with moderate to severe nausea:
a. At least 24 screening diary entries,
b. PAGI-SYM individual nausea score ≥ 2 at Visit 1,
c. Average daily diary nausea severity ≥ 2.5 during the screening period
d. At least one vomiting episode during screening period
Additional Inclusion Criteria for Group 2/Open Label Phase:
11. Diagnosed with diabetic, idiopathic, post-surgical or viral gastroparesis:
Presence of nausea at Visit 1 (PAGI-SYM individual nausea score ≥ 1 at Visit 1),
At least 24 screening diary entries,
Patients who do not qualify for Group 1/Evaluation Phase.
Another active disorder or treatment which could explain or contribute to symptoms in the opinion of the Investigator (including but not limited to gastric malignancy, neurological disorder, or heavy doses of strong anticholinergics);
Gastric or parenteral feeding within 4 weeks of screening;
Pregnancy or nursing;
History of intolerance and/or hypersensitivity to medications similar to tradipitant and its accompanying excipients;
History (including family history) or current evidence of congenital long QT syndrome or known acquired QT interval prolongation (including QTcF > 450 in males or > 470 in females at screening);
History of suicide attempt and/or suicidal ideation (of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS)) within 2 years of baseline or subject is at risk of suicide at Baseline visits, in the opinion of the investigator;
History of an eating disorder within 2 years of screening;
Recent history (within six months of screening) of Alcohol Use Disorder or Substance Use Disorder as defined in DSM-5 or evidence of such abuse which may include a positive drug screen at the Screening visit;
Uncontrolled thyroid disease;
Unstable cardiac, respiratory, hepatic or renal disease;
Indication of impaired liver function (including values for AST, ALT, or bilirubin > 2 times the Upper Limit of Normal, unless isolated bilirubin > 2 x ULN due solely to Gilbert’s syndrome) at screening;
Has a creatinine level > 2x ULN at screening;
Anyone affiliated with the site or sponsor and/or anyone who may consent under duress;
Any other reason as determined by the Investigator which may lead to an unfavorable risk-benefit of study participation, may interfere with study compliance, or may confound study results.
Additional Exclusion Criteria for Group 1/Evaluation Phase: Evidence of uncontrolled blood glucose (including HbA1C >9 for group 1 or HbA1C>10 for group 2 at screening or metabolic crisis in past 60 days);
Gastrectomy, fundoplication, vagotomy, pyloroplasty, bariatric surgery, or gastric stimulation device surgically implanted within the last year or if implanted more than a year ago, have changed stimulation settings within the last 3 months (ie gastric stimulation device must have a stable setting for at least 3 months);
Use of prohibited medication (See Section 5.2.1.) or medication with anti-nausea, antiemetic, neuromodulating, or prokinetic effect within 2 weeks of the screening visit EXCEPT when administered on a stable daily dosing schedule (stable for at least 3 months prior to the screening visit) or administered under protocol-specified rescue medication guidelines;
Use of the following within 2 weeks of screening: another NK-1 antagonist or a second generation 5-HT3 antagonist, phenergan more than 2 times per day, or opiods more than 2 times per week;
Pyloric injection of neurotoxins (e.g. botulinum type A or B) within 3 months of the Screening Visit;
Exposure to any investigational medication, including placebo or domperidone, within 60 days of the Baseline Visit.
Patients who previously participated in study VP-VLY-686-2301 or any other clinical study of tradipitant in the past.