Concentration-QT Study of Paroxetine in Healthy Adults

NCT06065735 | Completed Phase 1 Results

• 1 other identifier: 219882
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of the study is to evaluate the potential effect of paroxetine on QTc interval following escalating doses in healthy participants. Participants with no history of cardiac abnormalities or mood disorders will be enrolled. During the study, participants will take paroxetine at three incremental dose levels. Participants will attend the clinic at screening, baseline, at the end of each dose level administration week, and a final study exit visit. While on treatment outside of clinic visits, participants will be followed-up via video-call. A concentration-QTc analysis will assess any potential correlation between paroxetine plasma concentration and QTc prolongation. In addition, the occurrence of any side-effects will be compared between on and off treatment.

Conditions

Anxiety Disorders

Keywords

Dose escalation; QTc Interval; Paroxetine; Healthy Adults

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Corrected QT Interval by Fridericia (QTcF Interval)

  A standard 12-lead electrocardiogram (ECG) were recorded in a participant using an ECG machine after 10 minutes rest in the supine position. Baseline was defined as the sample obtained on Day -1. Change from Baseline was calculated by subtracting Baseline value from post dose value.

  Baseline (Day -1); 0.25 Hours Pre-dose on Day 1; 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12 Hours Post-dose on Day 1

Secondary Outcomes (7)

• Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Day -1) and Day 48

• Change From Baseline in Vital Sign: Pulse Rate

  Baseline (Day -1) and Day 48

• Change From Baseline in Vital Sign: Body Temperature

  Baseline (Day -1) and Day 48

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 48

• Number of Participants With Clinically Significant Findings for Hematology, Clinical Chemistry and Coagulation Laboratory Parameters

  Up to Day 48

Study Arms (1)

Paroxetine

EXPERIMENTAL

Drug: Paroxetine

Interventions

Paroxetine DRUG

Paroxetine will be administered

Paroxetine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants, both male and female, aged between 18 to 65 years, at the time of signing the informed consent.
• Participants determined as healthy based on medical evaluation by an experienced physician.
• A female participant is eligible to participate if she is of:
• Nonchildbearing potential defined as premenopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea.
• Child-bearing potential and agrees to use one of the contraception methods for an appropriate time as mentioned in the study protocol.
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin ≤ 1.5x (Upper Limit of Normal) ULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Body weight ≥ 45 kilogram (kg) and Body Mass Index (BMI) within the range 18 to 29.5 kilogram per metre square (kg/m2) (inclusive).
• No significant abnormality on 12-lead Electrocardiogram (ECG) at Screening in supine position, including the following specific requirements:
• Heart rate ≥ 40 beats per minute
• PR interval ≤ 220 milliseconds (msec) (For PR, QRS and QTcF interval, and Q wave, the mean of triplicate ECGs will be used)
• Q waves \< 50 msec (For PR, QRS and QTcF interval, and Q wave, the mean of triplicate ECGs will be used)
• QRS interval to be ≥ 60msec and \< 120msec (For PR, QRS and QTcF interval, and Q wave, the mean of triplicate ECGs will be used)
• The waveforms must enable the QT interval to be clearly defined
• QTcF interval must be \< 450msec (machine or manual reading).
• A signed and dated written informed consent obtained from participants capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• History or presence of any medically significant disease that may cause additional risk or interfere with the study procedures or outcome.
• History of symptomatic arrhythmias.
• History of hypersensitivity to paroxetine and excipients
• History of abnormal coagulation parameters, bleeding disorders or conditions which may predispose to bleeding.
• History of, or active suicidal ideation. Includes assessment using the Columbia Suicide Severity Rating Scale (C-SSRS)
• Must not have a pre-diagnosed mood disorder
• Participant is mentally or legally incapacitated.
• A supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHG) at Screening.
• A supine heart rate outside the range 50-90 beats per minute (bpm) at Screening.
• A positive screening Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
• A positive drug/alcohol screen at screening or prior to dosing.
• A positive test for Human Immune Virus (HIV) antibody at Screening.
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 millilitre \[ml\]) of beer, 1 glass (125ml) of wine or 1 (25 ml) measure of spirits.
• The participant has participated in a clinical trial and has received an investigational product within the following time prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2023
• First Posted: October 4, 2023
• Study Start: October 2, 2023
• Primary Completion: January 8, 2024
• Study Completion: January 8, 2024
• Last Updated: December 16, 2024
• Results First Posted: December 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

GB (1)