Phase 1
N=38
Concentration-QT Study of Paroxetine in Healthy Adults
Anxiety Disorders
Bottom Line
View on ClinicalTrials.gov: NCT06065735 ↗Enrolled (actual)
38
Serious AEs
1.0%
Results posted
Dec 2024
Primary outcome: Primary: Change From Baseline in Corrected QT Interval by Fridericia (QTcF Interval) — 1.9; 1.0; 0.9; 2.2 Milliseconds
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Paroxetine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jan 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Corrected QT Interval by Fridericia (QTcF Interval) |
1.9; 1.0; 0.9; 2.2; 2.9; 0.6 | — |
| SECONDARY Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
6.474; 4.763 | — |
| SECONDARY Change From Baseline in Vital Sign: Pulse Rate |
1.842 | — |
| SECONDARY Change From Baseline in Vital Sign: Body Temperature |
0.047 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
23; 19; 9; 1; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Findings for Hematology, Clinical Chemistry and Coagulation Laboratory Parameters |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Findings for Vital Signs |
0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Findings for Physical Examinations |
0; 0; 0 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 6 months with 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).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Use of the following medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of the study medication: monoamine oxidase inhibitors (including linezolid), thioridazine, pimozide, serotonergic drugs (including L-tryptophan, triptans, tramadol, selective serotonin reuptake inhibitors, lithium and fentanyl, tamoxifen, anti-coagulants, clozapine, phenothiazines, tricyclic antidepressants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs, Cox-2 inhibitors, antiarrhythmics, quinolone antibiotics, macrolides (including clarithromycin and erythromycin), ketoconazole and itraconazole
- Use of non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
- No current use of any medication other than paracetamol (doses ≤2 grams/day).
- Consumption of Seville oranges, pummelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication.
- Where participation in the study would result in donation of blood or blood products more than 500 mL within a 3-month period.
- Pregnant females as determined by positive serum β-HCG test at screening or serum/ urine beta-Human chorionic gonadotropin (HCG) prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Participants with unsuitable veins for cannulation and repeat venepuncture.
Data sourced from ClinicalTrials.gov (NCT06065735). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.