Back to results

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

Primary Purpose

Prader-Willi Syndrome

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CSTI-500

About this trial

This is an interventional other trial for Prader-Willi Syndrome focused on measuring PWS, Phase 1, Single Dose, Non randomized, PK, Safety

Eligibility Criteria

13 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CSTI-500 10mg

Arm Description

All eligible subjects will be administered a single oral dose of CSTI-500 10 mg at Visit 2

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax)

Maximum observed plasma concentration following drug administration determined directly from the concentration-time profile.

AUC0-72

Area under the plasma-drug concentration-time curve from pre-dose (time 0) to 72 hours after drug administration

AUC0-inf

Area under the plasma-drug concentration-time curve from pre-dose (time 0) extrapolated to infinite time

CSTI-500 plasma concentration

Secondary Outcome Measures

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.

Incidence of clinically significant findings in physical examinations

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.

Incidence of clinically significant findings in laboratory values

Laboratory evaluations include hematology, thyroid function, and chemistry blood and urine laboratory tests.

Incidence of clinically significant findings in 12-lead electrocardiograms (ECGs)

Comparison of CSTI-500 Cmax values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects

Comparison of CSTI-500 AUC0-72 values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects

Comparison of CSTI-500 AUC0-inf values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects

Full Information

NCT ID

NCT05504395

First Posted

August 4, 2022

Last Updated

August 8, 2023

Sponsor

ConSynance Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05504395

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

November 14, 2022 (Actual)

Primary Completion Date

February 21, 2023 (Actual)

Study Completion Date

February 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ConSynance Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prader-Willi Syndrome

Keywords

PWS, Phase 1, Single Dose, Non randomized, PK, Safety

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CSTI-500 10mg

Arm Type

Experimental

Arm Description

All eligible subjects will be administered a single oral dose of CSTI-500 10 mg at Visit 2

Intervention Type

Drug

Intervention Name(s)

CSTI-500

Other Intervention Name(s)

AMR-001181

Intervention Description

Single 10 mg capsule

Primary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax)

Description

Maximum observed plasma concentration following drug administration determined directly from the concentration-time profile.

Time Frame

Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

Title

AUC0-72

Description

Area under the plasma-drug concentration-time curve from pre-dose (time 0) to 72 hours after drug administration

Time Frame

Pre-dose to 1, 2, 4, 8, 12, 24, 48, and 72 hours post-dose

Title

AUC0-inf

Description

Area under the plasma-drug concentration-time curve from pre-dose (time 0) extrapolated to infinite time

Time Frame

Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

Title

CSTI-500 plasma concentration

Time Frame

1 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

2 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

4 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

8 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

12 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

24 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

48 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

72 hour post-dose

Title

CSTI-500 plasma concentration

Time Frame

144 hour post-dose

Secondary Outcome Measure Information:

Title

Incidence of treatment-emergent adverse events (TEAEs)

Description

Time Frame

From pre-dose to 15 days post-dose

Title

Incidence of clinically significant findings in physical examinations

Time Frame

Screening to 12, 24, 48, 72, and 144 hours post-dose

Title

Incidence of clinically significant findings in vital signs

Description

Time Frame

Screening and pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

Title

Incidence of clinically significant findings in laboratory values

Description

Laboratory evaluations include hematology, thyroid function, and chemistry blood and urine laboratory tests.

Time Frame

Screening to 24, 48, 72, and 144 hours post-dose

Title

Incidence of clinically significant findings in 12-lead electrocardiograms (ECGs)

Time Frame

Screening and pre-dose to 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

Title

Comparison of CSTI-500 Cmax values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects

Time Frame

Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

Title

Comparison of CSTI-500 AUC0-72 values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects

Time Frame

Pre-dose to 1, 2, 4, 8, 12, 24, 48, and 72 hours post-dose

Title

Comparison of CSTI-500 AUC0-inf values obtained from venous blood draws with values obtained from finger prick samples in PWS subjects

Time Frame

Pre-dose to 1, 2, 4, 8, 12, 24, 48, 72, and 144 hours post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Italo Biaggioni, MD

Organizational Affiliation

Vanderbilt Autonomic Dysfunction Center, Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs