Healthy Subjects
Conditions
Brief summary
The purpose of this study is to demonstrate a lack of effect of venlafaxine (Effexor XR) on QTc intervals relative to time matched placebo in healthy volunteers
Detailed description
This is a single-center, randomized, double-blinded, placebo- and moxifloxacin-controlled, 3 period, 6-sequence, 3 treatment (venlafaxine and placebo blinded; moxifloxacin open label), 3-way crossover thorough QT (TQT) study of the effects of venlafaxine on cardiac repolarization in approximately 54 healthy subjects
Interventions
DRUGVenlafaxine
Multiple doses of Venlafaxine for 14 days plus 3 days of down titration
DRUGMoxifloxacin
400 mg single dose moxifloxacin
DRUGDrug - placebo
Placebo administered for 16 days
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: 1. Healthy female subjects and/or male subjects who at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG or clinical laboratory tests. 2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs). 3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 4. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. 5. Based on CYP2D6 genotyping, the subject is required to be classified as a CYP2D6 extensive metabolizer (EM). Main
Exclusion criteria
1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). 2. Any condition possibly affecting drug absorption (eg, gastrectomy). 3. A positive urine drug screen. 4. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening. 5. Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study medication (whichever is longer). 6. Screening supine blood pressure \> 140 mm Hg (systolic) or \> 90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is \>140 mm Hg (systolic) or \>90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility. 7. Screening supine 12 lead ECG demonstrating QTcF \>450 msec or a QRS interval \>120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF or QRS values should be used to determine the subject's eligibility. 8. Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product or longer based upon the compound's half-life characteristics. 9. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. 10. As an exception, acetaminophen/paracetamol may be used at doses of less than 1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case by case basis following approval by the sponsor. Herbal supplements and hormone replacement therapy must be discontinued at least 28 days prior to the first dose of study medication. 11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing. 12. History of sensitivity to heparin or heparin induced thrombocytopenia. 13. History of known QTc prolongation or ECG abnormalities. 14. Individuals with known hypersensitivity reactions to venlafaxine, desvenlafaxine or SSRI (Selective serotonin reuptake inhibitors) or SNRI (Selective serotonin and norepinephrine reuptake inhibitors). 15. Individuals with a known hypersensitivity to moxifloxacin or quinolones.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Postdose QTcF (Fridericia's correction) intervals | 0 to 24 hours |
Secondary
| Measure | Time frame |
|---|---|
| Averse events, vital signs, physical examinations and abnormal laboratory for safety assessments (safety and tolerability) | Through the study completion, an average of 3 months |
| Relationship between QTc prolongation and the measured venlafaxine/desvenlafaxine plasma concentration | 0 to 24 hours |
Countries
United States
Outcome results
None listed