Study To Investigate The Potential Drug Drug Interaction (DDI) Between PF-00299804 And Paroxetine In Healthy Subjects

Study Overview
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Brief Summary
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Study of a drug drug interaction between Paroxetine and PF-00299804.

Official Title
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Phase 1 Single Dose Open Label Study To Investigate The Potential DDI Between PF-00299804 And Paroxetine In Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Period 1
* Drug: Period 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females of non-childbearing potential between the ages of 18 and 55 years, inclusive. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). An informed consent document signed and dated by the subject. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. Subjects must be extensive CYP2D6 metabolizers as determined by genotyping. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, dermatologic or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy). History of depression or other potential for increased suicidality with paroxetine. Family or personal medical history of prolonged QTc, congenital deafness or sudden death, or 12-lead ECG with QTc>450 msec. A positive urine drug screen, use of tobacco or nicotine-containing products, or regular alcohol consumption exceeding 14 drinks/ week for females or 21 drinks/week for men within prior 6 months. Pregnant or nursing females and females of childbearing potential including those with tubal ligation. Women of 45 to 55 years of age who are postmenopausal must have confirmatory FSH test results at screening. 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. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing. History of sensitivity to heparin or heparin-induced thrombocytopenia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DDI<br> | Drug: Period 1<br>* Subjects will receive a single 45 mg dose of PF-00299804 on Day 1 of Period 1.<br>Drug: Period 2<br>* Subjects will receive a single 30 mg tablet of paroxetine once daily for 3 days (Days 1 to 3). Then, subjects will be co-administered a 45 mg single dose of PF-00299804 plus a single dose of 30 mg paroxetine on Day 4. Single 30 mg doses of paroxetine will be administered once daily for 6 days (Days 5-10).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma AUCinf of PF-00299804 when given alone in healthy volunteers who are extensive CYP2D6 metabolizers |  | 8 weeks | 
| Plasma AUCt of PF-00299804 when given alone in healthy volunteers who are extensive CYP2D6 metabolizers |  | 8 weeks | 
| Plasma Cmax of PF-00299804 when given alone in healthy volunteers who are extensive CYP2D6 metabolizers |  | 8 weeks | 
| Plasma AUCinf of PF-00299804 when given in combination with paroxetine in healthy volunteers who are extensive CYP2D6 metabolizers |  | 8 weeks | 
| Plasma AUCt of PF-00299804 when given in combination with paroxetine in healthy volunteers who are extensive CYP2D6 metabolizers |  | 8 weeks | 
| Plasma Cmax of PF-00299804 when given in combination with paroxetine in healthy volunteers who are extensive CYP2D6 metabolizers |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma CL/F of PF-00299804 in EM without paroxetine. |  | 8 weeks | 
| Plasma Tmax of PF-00299804 in EM without paroxetine. |  | 8 weeks | 
| Plasma t1/2 of PF-00299804 in EM without paroxetine. |  | 8 weeks | 
| Plasma MRT of PF-00299804 in EM without paroxetine. |  | 8 weeks | 
| Plasma CL/F of PF-00299804 in EM with paroxetine. |  | 8 weeks | 
| Plasma Tmax of PF-00299804 in EM with paroxetine. |  | 8 weeks | 
| Plasma t1/2 of PF-00299804 in EM with paroxetine. |  | 8 weeks | 
| Plasma MRT of PF-00299804 in EM with paroxetine. |  | 8 weeks | 
| Plasma AUCinf of PF-05199265 in EMs when given alone (if levels permit). |  | 8 weeks | 
| Plasma AUCt of PF-05199265 in EMs when given alone (if levels permit). |  | 8 weeks | 
| Plasma Cmax of PF-05199265 in EMs when given alone (if levels permit). |  | 8 weeks | 
| Plasma Tmax of PF-05199265 in EMs when given in combination with paroxetine (if levels permit). |  | 8 weeks | 
| Plasma t1/2 of PF-05199265 in EMs when given in combination with paroxetine (if levels permit). |  | 8 weeks | 
| Overall safety profile as characterized by laboratory abnormalities, observed physical examination, vital signs, ECGs, and adverse event monitoring. |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DDI, Healthy Volunteers