A Pharmacokinetic and Safety Study of CSTI-500 in Subjects With Prader-Willi Syndrome

A Phase 1, Single Center, Open Label, Single Dose, Pharmacokinetic and Safety Study of CSTI-500 in Subjects With Prader-Willi Syndrome

The purpose of this Phase 1 study is to evaluate the pharmacokinetics (PK) and safety of a single dose of CSTI-500 10 mg in subjects with Prader-Willi syndrome (PWS) between 13 and 50 years of age with a genetically confirmed diagnosis of PWS.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: CSTI-500

Detailed Description

This is an open-label, single center, Phase 1 study to evaluate the PK and safety of a 10 mg single oral dose of CSTI-500, a triple monoamine reuptake inhibitor (TRI), in patients with genetically confirmed PWS. The study will consist of a Screening Period of up to 1-3 days prior to the Baseline Visit (Visit 2). In addition to the Screening Visit (Visit 1), eligible subjects will attend five in-clinic site visits for PK blood draws and safety assessments over a 6-day period. At Visit 2 all subjects will receive one single oral dose of CSTI-500 10 mg. Approximately 14 patients aged 13 to 50 years who meet all eligibility criteria will receive one single dose of CSTI-500.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female subjects (13-50 years of age at screening) with a documented medical record history of PWS confirmed by genetic testing.
• Subject must have a reliable caregiver/parent to bring the subject to the site for the visits, remain with the subject during visit times when allowed to be with the subject and respond to any questions during the visits.
• Female subjects must not be pregnant or lactating and be willing to use double barrier birth control method throughout the study.
• A normal supine systolic blood pressure must be ≤140 mmHg and ≥100 mmHg; diastolic blood pressure must be ≤80 mmHg and ≥60 mmHg at Screening. Pulse rate must be ≥50 bpm and ≤100 bpm and pulse rate increase on standing must be within acceptable range.
• All concomitant medications including blood pressure medications and type 2 diabetic medications must be stable for ≥3 months prior to screening (≤10% change). Supplements and vitamins are not considered concomitant medications for eligibility purposes.

Exclusion Criteria:

• Participation in any clinical study with an investigational drug/device within 3 months prior to screening or during the study.
• Recent use (within 3 months) of weight loss agents including prescription, herbal medications, and weight loss supplements.
• Major surgery within 6 months of screening or planned during the study or history of bariatric surgery.
• Any malignancy in the 2 years prior to screening (excluding basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated).
• Current liver, pulmonary, cardiac, or GI disease that would be expected to adversely affect study participation. Stable disease, e.g., asthma or controlled hypertension is not excluded. Liver disease or liver injury as indicated by abnormal liver function tests, ALT, AST, alkaline phosphatase, or serum bilirubin (≥3X ULN for any of these tests).
• Unexplained history or presence of combination of unexplained symptoms e.g., dizziness, syncope, fatigue, palpitations/tachycardia, headaches, or exercise intolerance.
• Heart failure classified per the New York Heart Association (NYHA) level II or greater.
• Myocardial infarction, stroke, or confirmed TIA within the last 5 years.
• Uncontrolled Type 2 diabetes as defined by HbA1c ≥ 9% at Screening.
• Insulin-dependent Type 1 diabetes.
• Subjects with a history of any suicidal behavior.
• Inability to swallow the oral capsule whole with water.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSTI-500 10mg; All eligible subjects will be administered a single oral dose of CSTI-500 10 mg at Visit 2	Drug: CSTI-500; Single 10 mg capsule; Other Names: AMR-001181

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration following drug administration determined directly from the concentration-time profile.	Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose
AUC0-72	Area under the plasma-drug concentration-time curve from pre-dose (time 0) to 72 hours after drug administration	Pre-dose to 1, 2, 4, 8, 12, 24, 48, and 72 hours post-dose
AUC0-inf	Area under the plasma-drug concentration-time curve from pre-dose (time 0) extrapolated to infinite time	Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose
CSTI-500 plasma concentration		1 hour post-dose
CSTI-500 plasma concentration		2 hour post-dose
CSTI-500 plasma concentration		4 hour post-dose
CSTI-500 plasma concentration		8 hour post-dose
CSTI-500 plasma concentration		12 hour post-dose
CSTI-500 plasma concentration		24 hour post-dose
CSTI-500 plasma concentration		48 hour post-dose
CSTI-500 plasma concentration		72 hour post-dose
CSTI-500 plasma concentration		144 hour post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Number of participants with TEAEs, defined as an adverse event (AE) that is new or worsened in severity after the dose of study drug. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will be summarized by system organ class, preferred term, and treatment.	From pre-dose to 15 days post-dose
Incidence of clinically significant findings in physical examinations		Screening to 12, 24, 48, 72, and 144 hours post-dose
Incidence of clinically significant findings in vital signs	Participants will be assessed for any clinically significant changes in vital parameters (blood pressure, heart rate in supine and standing position, respiratory rate, and body temperature). This also includes evaluation of postural orthostatic tachycardic syndrome.	Screening and pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose
Incidence of clinically significant findings in laboratory values	Laboratory evaluations include hematology, thyroid function, and chemistry blood and urine laboratory tests.	Screening to 24, 48, 72, and 144 hours post-dose
Incidence of clinically significant findings in 12-lead electrocardiograms (ECGs)		Screening and pre-dose to 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose
Comparison of CSTI-500 Cmax values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects		Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose
Comparison of CSTI-500 AUC0-72 values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects		Pre-dose to 1, 2, 4, 8, 12, 24, 48, and 72 hours post-dose
Comparison of CSTI-500 AUC0-inf values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects		Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

Collaborators and Investigators

• Sponsor: ConSynance Therapeutics
• Investigators: Principal Investigator: Italo Biaggioni, MD, Vanderbilt Autonomic Dysfunction Center, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Actual): February 21, 2023
• Study Completion (Actual): February 21, 2023

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Safety; PK; Phase 1; PWS; Single Dose; Non randomized
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: CSTI-500-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No