A TQT Study to Evaluate the Electrocardiographic Effects of Carbidopa in Healthy Subjects

A Three-Way Crossover Thorough QT/QTc Study to Evaluate the Electrocardiographic Effects of a Supratherapeutic Dose of Carbidopa in Healthy Subjects

The purpose of this trial is to assess the effects of a single supratherapeutic dose of carbidopa on cardiac repolarization relative to placebo in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Cardiac Repolarization in Healthy Subjects
• Intervention / Treatment: Drug: Carbidopa capsule; Drug: Moxifloxacin Tablets, USP; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hester Visser; Phone Number: 631-438-9258; Email: Hester.Visser@amneal.com
• Study Contact Backup: Name: Pam Fitzpatrick; Phone Number: 631-559-2637; Email: pfitzpatrick@amneal.com

Study Locations

• United States
  • Minnesota
    • Dilworth, Minnesota, United States, 56529-1342
      • AXIS Clinicals, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males and females aged 18 to 55 years (both inclusive)
• For female subjects of childbearing potential, use of double contraception method
• Body Mass Index (BMI) 18.5 to <30 kg/m² at Screening, with a minimum weight of 55kg
• Subject with no clinically significant abnormal serum biochemistry, hematology and urine examination values at screening
• Subject with negative urine screen for drugs of abuse at screening
• Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results at screening
• Subject must be willing to communicate with the investigator and site staff and comply with all study procedures and requirements
• Subject must be able to provide written, informed consent including compliance with the requirements listed in the consent form
• Subject must be able and willing to swallow whole capsules without breaking, cutting, or chewing

Exclusion Criteria:

• History or presence of systemic diseases at Screening, which as judged by the investigator, may affect the outcome of this study, include, but not limited to significant: cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• Female subjects who are pregnant or lactating
• Knowledge of any kind of cardiovascular disorder/condition known to increase the possibility of QT prolongation or history of additional risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome or Brugada Syndrome) or cardiac conduction disorders
• Resting supine heart rate less than 50 beats per minute or greater than 100 beats per minute
• Resting supine systolic blood pressure less than 90 mmHg or greater than 140 mmHg; resting supine diastolic blood pressure less than 50 mmHg or greater than 90 mmHg.

• Clinically significant (as determined by the Investigator) ECG abnormalities at Screening, including:

  1. QTcF > 450 ms for female and >430 ms for male
  2. QRS > 110 ms
  3. PR > 200 ms
  4. QTcF > 450 ms for female and >430 for male
  5. QRS > 110 ms
  6. PR > 200 ms
  7. Resting supine HR <50 beats per minute (bpm) or >100 bpm (may be repeated once at the discretion of the investigator)
  8. Second or third-degree AV block
  9. Any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant
  10. Bundle Branch Block
  11. premature atrial and ventricular contractions,
  12. nonspecific T-wave changes
• Positive urine/serum drug screen at Screening or Day -1 for each Period
• History of significant alcohol abuse or drug abuse within one year prior to Screening.
• Use of prescription medication (with the exception of medically approved hormonal contraceptives) including MAO inhibitors in the 30 days prior to admission into Period 1 and over-the-counter medications including vaccines, vitamins, and herbal remedies within 14 days prior to admission of Period 1 till completion of the study (EOS or ET)
• History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations or near drowning with hospital admission
• Subjects who received any investigational drug within the longer of 30 days or 5 half-lives of Day 1 dosing of SM
• Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study
• Use of medications in the 90 days before admission of the study that are known to prolong the QT/QTc interval.
• Family history of QTc prolongation or of unexplainable sudden death at <50 years of age. For this study, family is defined as 1st degree relative (i.e., mother, father, siblings, children) or 2nd degree relative (grandparents, grandchildren, half-siblings, aunt/uncle, niece/nephew).
• Subjects who cannot refrain from using tobacco of any kind within 30 days prior to admission (Day -1) of Period 1 until the last blood sample collection of study
• Subjects who cannot refrain from consumption of alcohol or alcohol containing products or xanthine-containing foods or beverages (like chocolate, tea, coffee or cola drinks) within 48 hours prior to admission (Day -1) of Period 1 till the last blood sample collection of study
• Subjects who participate in other drug research study during the study.
• Subjects who cannot refrain from donating blood or plasma for 30 days and 14 days (respectively) prior to dosing, during the study, and for at least 4 weeks after completing the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Carbidopa capsule; Dose: 4x 100 mg; Drug: Moxifloxacin Tablets, USP; Dose: 400 mg; Drug: Placebo; Placebo capsules matching the carbidopa capsules
Experimental: Carbidopa capsule; Dose: 4x 100 mg	Drug: Carbidopa capsule; Dose: 4x 100 mg; Drug: Moxifloxacin Tablets, USP; Dose: 400 mg; Drug: Placebo; Placebo capsules matching the carbidopa capsules
Active Comparator: Moxifloxacin Tablets, USP; Dose: 400 mg	Drug: Carbidopa capsule; Dose: 4x 100 mg; Drug: Moxifloxacin Tablets, USP; Dose: 400 mg; Drug: Placebo; Placebo capsules matching the carbidopa capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline QTcF (ΔQTcF)	Change-from-baseline QTcF ( QTcF) will allow evaluation of the effects of carbidopa and moxifloxacin on cardiac repolarization based on model derived placebo-corrected ΔQTcF (ΔΔQTcF).	Predose to 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline HR, PR, and QRS	Change from baseline HR, PR, and QRS (ΔHR, ΔPR, ΔQRS) will also be measured to allow evaluation of the effects of carbidopa and moxifloxacin on other ECG parameters based on model derived placebo-corrected ΔHR, ΔPR, and ΔQRS (ΔΔHR, ΔΔPR, and ΔΔQRS).	Predose to 24 hours postdose

Collaborators and Investigators

• Sponsor: Impax Laboratories, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): December 3, 2023
• Study Completion (Actual): December 5, 2023

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Moxifloxacin; Carbidopa
• Other Study ID Numbers: IPX203-102-23

Drug and device information, study documents

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