Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 93 of 205 for:    SPORANOX I.V. OR ITRACONAZOLE OR ONMEL OR SPORANOX-PULSE OR Sporanos OR R 51,211 OR SPORANOX

A Study to Estimate the Effect of CYP3A4 Inhibitors (Itraconazole, Diltiazem or Verapamil) on the Pharmacokinetics of Single Dose PF- 00489791 in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02319148
Recruitment Status : Completed
First Posted : December 18, 2014
Results First Posted : September 16, 2016
Last Update Posted : September 16, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Healthy Volunteers
Interventions Drug: itraconazole
Drug: diltiazem
Drug: SR verapamil
Drug: PF-00489791
Enrollment 22
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1. All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2. All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2 All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Period Title: First Intervention Period
Started 22 0 0 0
Completed 22 0 0 0
Not Completed 0 0 0 0
Period Title: Washout Period 4 Days
Started 22 0 0 0
Completed 22 0 0 0
Not Completed 0 0 0 0
Period Title: Second Intervention Period
Started 0 7 7 8
Completed 0 6 6 6
Not Completed 0 1 1 2
Reason Not Completed
Adverse event (AE) related to study drug             0             0             1             1
No longer willing to participate             0             1             0             0
Other             0             0             0             1
Arm/Group Title PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg Total
Hide Arm/Group Description All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2. All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2 All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2. Total of all reporting groups
Overall Number of Baseline Participants 7 7 8 22
Hide Baseline Analysis Population Description
The baseline analysis population included all eligible participants who received a single dose of PF-00489791 20 mg tablet orally.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 7 participants 8 participants 22 participants
38.1  (6.1) 33.4  (9.9) 35.1  (10.1) 35.5  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 8 participants 22 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
7
 100.0%
7
 100.0%
8
 100.0%
22
 100.0%
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of PF-00489791
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
1140
(34%)
1238
(33%)
1198
(33%)
1186
(21%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Itraconazole 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 105.28
Confidence Interval (2-Sided) 90%
92.11 to 120.34
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Diltiazem 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 92.54
Confidence Interval (2-Sided) 90%
80.96 to 105.77
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Verapamil 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 116.36
Confidence Interval (2-Sided) 90%
101.86 to 132.92
Estimation Comments [Not Specified]
2.Primary Outcome
Title Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-00489791
Hide Description AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour per milliliter (ng*hr/mL)
17880
(36%)
18140
(24%)
16840
(20%)
19560
(30%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Itraconazole 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 90.16
Confidence Interval (2-Sided) 90%
78.57 to 103.46
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Diltiazem 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 106.38
Confidence Interval (2-Sided) 90%
92.70 to 122.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Verapamil 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 101.71
Confidence Interval (2-Sided) 90%
88.68 to 116.66
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00489791
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.hr/mL
17580
(36%)
17980
(24%)
16760
(20%)
19400
(30%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Itraconazole 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 91.33
Confidence Interval (2-Sided) 90%
79.49 to 104.94
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Diltiazem 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 106.97
Confidence Interval (2-Sided) 90%
93.10 to 122.91
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-00489791 20 mg, PF-00489791 20 mg + Verapamil 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 102.69
Confidence Interval (2-Sided) 90%
89.42 to 117.93
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00489791
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Median (Full Range)
Unit of Measure: hour
4.00
(2.00 to 4.08)
3.50
(2.00 to 4.00)
4.00
(1.00 to 4.00)
4.00
(2.00 to 4.07)
5.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of PF-00489791
Hide Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter
18.06
(34%)
21.65
(18%)
19.98
(31%)
19.23
(23%)
6.Secondary Outcome
Title Apparent Oral Clearance (CL/F) of PF-00489791
Hide Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: milliliter per minute (mL/min)
18.64
(36%)
18.37
(24%)
19.81
(20%)
17.02
(30%)
7.Secondary Outcome
Title Terminal Elimination Half-Life (t1/2) of PF-00489791
Hide Description t1/2 is the time measured for the plasma concentration to decrease by one half.
Time Frame Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Mean (Standard Deviation)
Unit of Measure: hour
11.39  (2.15) 13.85  (2.79) 11.75  (1.69) 13.29  (2.56)
8.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
Hide Description The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, RBC morphology, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (coagulation panel, circulating immune complex, and complement activation).
Time Frame Baseline up to 28 days after last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received the study medication.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Measure Type: Number
Unit of Measure: participants
3 0 0 2
9.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Vital Signs Findings
Hide Description Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of >=30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mmHg change from baseline in same posture or DBP <50 mm Hg.
Time Frame Baseline up to Day 9
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received the study medication; n=number of participants evaluated against criteria.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 7 7 8
Measure Type: Number
Unit of Measure: participants
Supine SBP <90 mm Hg (n=22,7,7,8) 0 0 0 1
Standing SBP <90 mm Hg (n=22,7,6,8) 0 0 0 1
Supine DBP <50 mm Hg (n=22,7,7,8) 0 0 0 0
Standing DBP <50 mm Hg (n=22,7,6,8) 0 0 0 1
Supine Pulse Rate <40 or >120 bpm (n=22,7,7,8) 0 0 0 0
Standing Pulse Rate <40 or >120 bpm (n=22,7,6,8) 0 0 0 0
Supine SBP >=30 mm Hg IFB (n=22,6,6,7) 0 0 0 0
Standing SBP >=30 mm Hg IFB (n=22,6,6,7) 0 0 0 0
Supine DBP >=20 mm Hg IFB (n=22,6,6,7) 0 0 0 0
Standing DBP >=20 mm Hg IFB (n=22,6,6,7) 0 0 0 0
Supine SBP >=30 mm Hg DFB (n=22,6,6,7) 0 0 0 0
Standing SBP >=30 mm Hg DFB (n=22,6,6,7) 0 0 1 1
Supine DBP >=20 mm Hg DFB (n=22,6,6,7) 0 0 0 0
Standing DBP >=20 mm Hg DFB (n=22,6,6,7) 1 0 1 1
10.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Hide Description ECG parameters included PR interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (>=)300 milliseconds (msec) or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QRS interval >=140 msec or >=50% increase from baseline (IFB); and QTcF >=450 msec or >=30 msec increase. The number of participants with potentially clinically significant ECG findings at any visit were reported.
Time Frame Pre-dose (Periods 1 and 2), 4, 72 and 96 hours post-dose in Period 2
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received the study medication; n=number of participants evaluated against criteria.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 7 7 8
Measure Type: Number
Unit of Measure: participants
PR Interval >=300 msec (n=22,7,7,8) 0 0 0 0
QRS Complex >=140 msec (n=22,7,7,8) 0 0 0 0
QTcF Interval 450-<480 msec (n=22,7,7,8) 0 0 0 0
QTcF Interval 480-<500 msec (n=22,7,7,8) 0 0 0 0
QTcF Interval >=500 msec (n=22,7,7,8) 0 0 0 0
PR Interval >=25/50% IFB (n=22,6,6,7) 0 0 0 0
QRS Interval >=50% IFB (n=22,6,6,7) 0 0 0 0
QTcF Interval 30-<60 msec IFB (n=22,6,6,7) 0 1 0 0
QTcF Interval >=60 msec IFB (n=22,6,6,7) 0 0 0 0
11.Secondary Outcome
Title Number of Participants Who Used at Least 1 Concomitant Medication
Hide Description Participants were to abstain from all concomitant treatments, except for the treatment of AEs. Treatments taken after the first dose of study treatment were documented as concomitant treatments.
Time Frame Baseline up to Day 15 (final study evaluation)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received the study medication.
Arm/Group Title PF-00489791 20 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 6 6 6
Measure Type: Number
Unit of Measure: participants
Drug Treatments 10 2 4 2
Non-Drug Treatments 0 0 0 0
12.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Time Frame Baseline up to 28 days after last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received the study medication.
Arm/Group Title PF-00489791 20 mg Itraconazole 200 mg Diltiazem 240 mg Verapamil 240 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description:
All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1.
All participants who received itraconazole 200 mg orally once daily for 7 days.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days.
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days.
All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2.
All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2
All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
Overall Number of Participants Analyzed 22 7 7 8 6 6 6
Measure Type: Number
Unit of Measure: participants
AEs 18 6 4 3 6 4 5
SAEs 0 0 0 0 0 0 0
Time Frame Baseline up to 28 days after last study drug administration
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title PF-00489791 20 mg Itraconazole 200 mg Diltiazem 240 mg Verapamil 240 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Hide Arm/Group Description All participants who received a single-dose of PF-00489791 20 mg tablet orally during Period 1. All participants who received itraconazole 200 mg orally once daily for 7 days. All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days. All participants who received verapamil 240 mg SR tablet orally once daily for 13 days. All participants who received itraconazole 200 mg orally once daily for 7 days and a single-dose of PF-00489791 20 mg on Day 5 during Period 2. All participants who received diltiazem 240 mg MR tablet orally once daily for 13 days and a single-dose of PF-00489791 20mg on Day 11 during Period 2 All participants who received verapamil 240 mg SR tablet orally once daily for 13 days and a single-dose of PF-00489791 20 mg on Day 11 during Period 2.
All-Cause Mortality
PF-00489791 20 mg Itraconazole 200 mg Diltiazem 240 mg Verapamil 240 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
PF-00489791 20 mg Itraconazole 200 mg Diltiazem 240 mg Verapamil 240 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/22 (0.00%)      0/7 (0.00%)      0/7 (0.00%)      0/8 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-00489791 20 mg Itraconazole 200 mg Diltiazem 240 mg Verapamil 240 mg PF-00489791 20 mg + Itraconazole 200 mg PF-00489791 20 mg + Diltiazem 240 mg PF-00489791 20 mg + Verapamil 240 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/22 (81.82%)      6/7 (85.71%)      4/7 (57.14%)      3/8 (37.50%)      6/6 (100.00%)      4/6 (66.67%)      5/6 (83.33%)    
Cardiac disorders               
Palpitations * 1  0/22 (0.00%)  0/7 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders               
Abdominal discomfort * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%) 
Abdominal distension * 1  0/22 (0.00%)  2/7 (28.57%)  2/7 (28.57%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Diarrhoea * 1  0/22 (0.00%)  1/7 (14.29%)  0/7 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Dyspepsia * 1  2/22 (9.09%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Flatulence * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Nausea * 1  5/22 (22.73%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%) 
Vomiting * 1  3/22 (13.64%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
General disorders               
Fatigue * 1  2/22 (9.09%)  0/7 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Investigations               
Alanine aminotransferase increased * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia * 1  0/22 (0.00%)  0 0/7 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Back pain * 1  8/22 (36.36%)  4/7 (57.14%)  0/7 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Muscle spasms * 1  4/22 (18.18%)  0/7 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Neck pain * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Sensation of heaviness * 1  2/22 (9.09%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Myalgia * 1  3/22 (13.64%)  1/7 (14.29%)  1/7 (14.29%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%) 
Nervous system disorders               
Dizziness * 1  2/22 (9.09%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Head discomfort * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%) 
Headache * 1  14/22 (63.64%)  1/7 (14.29%)  4/7 (57.14%)  2/8 (25.00%)  6/6 (100.00%)  4/6 (66.67%)  2/6 (33.33%) 
Psychiatric disorders               
Irritability * 1  1/22 (4.55%)  0/7 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Renal and urinary disorders               
Nocturia * 1  0/22 (0.00%)  1/7 (14.29%)  0/7 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Polyuria * 1  1/22 (4.55%)  1/7 (14.29%)  0/7 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Reproductive system and breast disorders               
Spontaneous penile erection * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  1/6 (16.67%) 
Skin and subcutaneous tissue disorders               
Rash * 1  0/22 (0.00%)  0/7 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Vascular disorders               
Haematoma * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Hot flush * 1  3/22 (13.64%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  5/6 (83.33%)  2/6 (33.33%)  1/6 (16.67%) 
Orthostatic hypotension * 1  0/22 (0.00%)  0/7 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02319148     History of Changes
Other Study ID Numbers: A7331022
2014-001979-31 ( EudraCT Number )
First Submitted: September 17, 2014
First Posted: December 18, 2014
Results First Submitted: October 5, 2015
Results First Posted: September 16, 2016
Last Update Posted: September 16, 2016