A Multicenter Open Label 3 Month Safety Study with Tradipitant in Patients with Idiopathic or Diabetic Gastroparesis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vanda Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

29 Nov 2023 → 31 Mar 2026

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Vanda Pharmaceuticals Inc.

External identifiers

EU CT number

2023-503802-35-00

EudraCT number

2022-001511-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenomic, Safety, Efficacy, Therapy

To evaluate dosing of tradipitant on standard measures of subject safety

Secondary objectives 3

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

Conditions and MedDRA coding

Idiopathic or diabetic gastroparesis with moderate to severe nausea.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Male and female subjects aged 18 – 70 years (inclusive)
2. 2. 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
3. 3. Patient's gastroparesis symptoms persist despite diet and/or life-style modifications
4. 4. Body Mass Index (BMI) of ≥18 and ≤ 40 kg/m2 (BMI = weight (kg)/ [height (m)]2)
5. 5. 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
6. 6. Ability and acceptance to provide written informed consent
7. 7. Willing to participate in the pharmacogenomics sample collection
8. 8. 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)
9. 9. Willing to not participate in any other interventional trial for the duration of their participation
10. 10. 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.

Exclusion criteria 19

1. 1. 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)
2. 18. 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);
3. 2. The inability to take the study medication
4. 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.
5. 3. Pregnancy or nursing
6. 4. History of intolerance and/or hypersensitivity to medications similar to tradipitant and its accompanying excipients
7. 5. 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)
8. 6. 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
9. 7. History of an eating disorder within 2 years of first study visit
10. 8. 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
11. 10. Unstable cardiac, respiratory, hepatic or renal disease
12. 9. Uncontrolled thyroid disease
13. 11. 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)
14. 12. Has a creatinine level > 2x ULN
15. 13. 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
16. 14. Use of the following within 2 weeks of first study visit: another NK-1 antagonist or a second generation 5-HT3 antagonist
17. 15. Evidence of uncontrolled blood glucose (including HbA1C >11% at screening or metabolic crisis in past 60 days)
18. 16. 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)
19. 17. Pyloric injection of neurotoxins (e.g. botulinum type A or B) within 1 month of the first study visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate dosing of tradipitant on standard measures of subject safety by assessing adverse events (AEs) including suicidal ideation or behavior, changes in vital signs, clinical laboratory evaluations, electrocardiograms (ECGs) and physical exam findings during treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vanda Pharmaceuticals Inc.

Sponsor organisation

Vanda Pharmaceuticals Inc.

Address

2200 Pennsylvania Avenue Northwest Suite 300

City

Washington

Postcode

20037-1709

Country

United States

Scientific contact point

Organisation

Vanda Pharmaceuticals Inc.

Contact name

Jesse L. Carlin

Public contact point

Organisation

Vanda Pharmaceuticals Inc.

Contact name

Jesse L. Carlin

Third parties 1

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications