Safety Evaluation of Tradipitant in Patients with Idiopathic or Diabetic Gastroparesis: A Multicenter, Open-Label, 3-Month Study

Trial ID: 2023-503802-35-00
Protocol: VP-VLY-686-3304
Sponsor: Vanda Pharmaceuticals Inc.

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Diseases & Conditions

Impaired gastric emptying Diabetic gastroparesis

Objectives

The primary objective of this study is to evaluate the **dosing** of tradipitant on standard measures of subject safety in patients with idiopathic or diabetic **gastroparesis** with moderate to severe nausea. This is clinically relevant as it aims to ensure the safe administration of tradipitant, a critical factor in the management of gastroparesis, a condition characterized by delayed gastric emptying and associated with significant morbidity.

Secondary objectives include:

To evaluate the efficacy of tradipitant in reducing individual symptoms associated with gastroparesis.
To evaluate the efficacy of tradipitant in global improvement and quality of life measures.
To study the etiology and variability of clinical expression in gastroparesis.

Participants

The clinical trial focuses on evaluating the dosing of tradipitant in subjects diagnosed with **idiopathic or diabetic gastroparesis** accompanied by moderate to severe nausea. The study population includes both male and female participants aged between 18 and 70 years. Participants are required to have a Body Mass Index (BMI) ranging from 18 to 40 kg/m². The trial population was selected based on the persistence of gastroparesis symptoms despite dietary and lifestyle modifications. Participants must demonstrate delayed gastric emptying and have experienced nausea symptoms for at least six months prior to screening. The study includes individuals who are willing to comply with study requirements, including daily symptom diary completion and strict control of blood glucose for those with Type 1 or Type 2 diabetes mellitus. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed as a **multicenter open-label** study to evaluate the safety of **tradipitant** in patients diagnosed with idiopathic or diabetic **gastroparesis** experiencing moderate to severe nausea. The primary objective is to assess the dosing of tradipitant on standard measures of subject safety, including adverse events, changes in vital signs, clinical laboratory evaluations, electrocardiograms, and physical exam findings during treatment. The trial is expected to last for a total duration of 12 weeks, with participant involvement spanning the same period. The study will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, diagnosis, and symptom severity. Participants will be required to demonstrate delayed gastric emptying and persistent symptoms despite dietary or lifestyle modifications.

Following the screening, eligible participants will be enrolled and will undergo a series of study visits. These visits will include regular assessments to monitor safety and adherence to study protocols. Participants will be required to maintain a daily symptom diary and adhere to study restrictions, including the use of contraception and avoidance of prohibited medications. The study will conclude with an end-of-study visit, where final evaluations will be conducted to assess the overall safety profile of tradipitant. Conditions that may lead to early termination from the study include non-compliance with study requirements, the occurrence of significant adverse events, or withdrawal of consent by the participant. The trial is not categorized as low intervention and is conducted under the sponsorship of Vanda Pharmaceuticals Inc., with the investigational product administered orally in capsule form.

Treatment

The clinical trial involves the administration of the experimental medication **VLY-686**, which contains the active substance **tradipitant**. This medication is provided in the form of a **capsule** and is intended for oral administration. The maximum daily dose of VLY-686 is 170 mg, and the treatment period is set for a maximum of 12 weeks. The medication is of chemical origin and is not formulated specifically for pediatric use. The primary objective of the trial is to evaluate the dosing of tradipitant on standard measures of subject safety in patients with idiopathic or diabetic gastroparesis.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is designed as an open-label study, meaning that both the researchers and participants are aware of the treatment being administered. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. The trial aims to gather safety data over a three-month period, providing insights into the safety profile of tradipitant in the specified patient population.

Efficacy

The clinical trial aims to assess the efficacy of **tradipitant** in patients with idiopathic or diabetic gastroparesis. Efficacy will be evaluated through the measurement of symptom improvement, specifically focusing on nausea, which is a cardinal symptom of gastroparesis. Participants are required to have a PAGI-SYM individual nausea score of at least 1 at Visit 1 and must report at least two cardinal symptoms of gastroparesis, such as nausea, vomiting, excessive fullness, early satiety, bloating, or upper abdominal pain, with an average severity greater than mild. Additionally, participants must have at least one vomiting episode as recorded in a daily symptom diary during the screening period.

The primary endpoint for efficacy assessment involves the evaluation of dosing of tradipitant on standard measures of subject safety, including adverse events, changes in vital signs, clinical laboratory evaluations, electrocardiograms (ECGs), and physical exam findings during treatment. The trial will utilize validated scales and patient-reported outcomes to collect data on symptom severity and frequency. The schedule for measuring these parameters will be aligned with the trial visits, ensuring consistent and reliable data collection throughout the study duration.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male and female subjects aged 18 – 70 years (inclusive)
Diagnosed with idiopathic or diabetic gastroparesis with moderate to severe nausea: a. Demonstrated delayed gastric emptying of a solid meal via either scintigraphy, gastric breath test, or wireless motility capsule within 10 years of screening of prior study. 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 of prior study
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:a. Males of procreative capacity (not surgically sterile) will use an acceptable method of contraception from first study visit 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; b. Females of child-bearing potential (not surgically sterile or postmenopausal, defined as 12 months without menses) will use an acceptable method of contraception from 1 month prior to first study visit 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: a. Daily symptom diary completion, b. Prohibited medications, and c. strict control of blood glucose (T1DM and T2DM patients)
Willing to not participate in any other interventional trial for the duration of their participation
Diagnosed with idiopathic or diabetic gastroparesis with the presence of nausea symptom: a. Atleast 24 daily diary entries b. PAGI-SYM individual nausea score ≥ 1 at Visit 1 c. The presence of atleast 2 cardinal symptoms of gastroparesis averaging greater than mild including ≥ 2 average severity in nausea, vomiting, excessive fullness, early satiety, bloating or upper abdominal pain or ≥ 1 vomiting episodes as measured by the daily symptom diary during the screening period.

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Exclusion Criteria

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)
Exposure to any other investigational medication, including a placebo within 60 days of first study visit. Domperidone is allowable within the study if approved for use under national regulatory body guidelines and if taken up to recommended dosing of 10-20mg up to 4 times a day (up to 80mg per day);
The inability to take the study medication
19.Any other reason as determined by the Investigator which may lead to an unfavorable riskbenefit of study participation, may interfere with study compliance, or may confound study results.
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 QTc > 450 in males or > 470 in females at first study visit)
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 first study visit or subject is at risk of suicide at first study visit, in the opinion of the investigator
History of an eating disorder within 2 years of first study visit
Recent history (within six months of first study visit) 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 first study visit and does not include medical marijuana use
Unstable cardiac, respiratory, hepatic or renal disease
Uncontrolled thyroid disease
Indication of impaired liver function (including values for AST, ALT, or bilirubin > 2x times the Upper Limit of Normal, unless isolated bilirubin > 2 x ULN due solely to Gilbert's syndrome)
Has a creatinine level > 2x ULN
Use of prohibited medication or medication with anti-nausea,antiemetic, neuromodulating, or prokinetic effect within 2 weeks of the first study visit EXCEPT when administered on a stable daily dosing schedule (stable for at least 3 months prior to first study visit) or administered under protocol-specified rescue medication guidelines
Use of the following within 2 weeks of first study visit: another NK-1 antagonist or a second generation 5-HT3 antagonist
Evidence of uncontrolled blood glucose (including HbA1C >11% at screening or metabolic crisis in past 60 days)
Surgeries to the stomach including gastrectomy, fundoplication, vagotomy, pyloroplasty, bariatric surgery, or gastric stimulation device surgically implanted in the last 2 months from screening or if gastric stimulation device surgically implanted, have changed stimulation settings within the last 1 months (ie gastric stimulation device must have a stable setting for at least 1 months)
Pyloric injection of neurotoxins (e.g. botulinum type A or B) within 1 month of the first study visit