A Study to Estimate the Effect of CYP3A4 Inhibitors (Itraconazole, Diltiazem or Verapamil) on the Pharmacokinetics of Single Dose PF- 00489791 in Healthy Volunteers
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02319148
Collaborator
(none)
22
1
3
3
7.3
Study Details
Study Description
Brief Summary
The primary objective of the study is to estimate the effects of different strong enzyme (CYP3A4) inhibitors, itraconazole, diltiazem, or verapamil on the single dose pharmacokinetics of PF-00489791 in healthy volunteers. The study will enroll approximately 18 subjects that are randomized to 1 of 3 treatment groups. The study is also intended to determine the safety and tolerability of single-dose PF- 00489791 when it is administered with steady-state itraconazole, diltiazem, or verapamil.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
22 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A Phase 1, Randomized, Open-label, 3-sequence, 4-treatment, Incomplete Block Design To Estimate The Effect Of Steady State Cyp3a4 Inhibitors (Itraconazole, Diltiazem Or Verapamil) On The Pharmacokinetics Of Singe Dose Pf-00489791 In Healthy Volunteers
Study Start Date
:
Jul 1, 2014
Actual Primary Completion Date
:
Oct 1, 2014
Actual Study Completion Date
:
Oct 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment B Treatment B subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of itraconazole (200 mg once daily). |
Drug: itraconazole
itraconazole dosed at 200 mg
Drug: PF-00489791
PF-00489791 20 mg single dose administration
|
| Experimental: Treatment C Treatment C subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of diltiazem (240 mg once daily). |
Drug: diltiazem
diltiazem dosed at 240 mg
Drug: PF-00489791
PF-00489791 20 mg single dose administration
|
| Experimental: Treatment D Treatment D subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of verapamil (240 mg once daily). |
Drug: SR verapamil
SR verapamil dosed at 240 mg
Drug: PF-00489791
PF-00489791 20 mg single dose administration
|
Outcome Measures
Primary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
- Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
Secondary Outcome Measures
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
- Apparent Volume of Distribution (Vz/F) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
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.
- Apparent Oral Clearance (CL/F) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
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.
- Terminal Elimination Half-Life (t1/2) of PF-00489791 [Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration]
t1/2 is the time measured for the plasma concentration to decrease by one half.
- Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern [Baseline up to 28 days after last study drug administration]
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).
- Number of Participants With Potentially Clinically Significant Vital Signs Findings [Baseline up to Day 9]
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.
- Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [Pre-dose (Periods 1 and 2), 4, 72 and 96 hours post-dose in Period 2]
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.
- Number of Participants Who Used at Least 1 Concomitant Medication [Baseline up to Day 15 (final study evaluation)]
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.
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to 28 days after last study drug administration]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Healthy male and/or female subjects 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 and clinical laboratory tests) with a Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs.) and with a personally signed and dated informed consent document and who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
-
Participating female subjects of non-childbearing potential must meet at least one of the following criteria: achieved postmenopausal status; have undergone a documented hysterectomy and/or bilateral oophorectomy; have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.
Exclusion Criteria:
-
Subjects cannot be included in the study if there is: the presence/ history of any disorder that prevents study completion
-
Evidence/history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
-
Any surgical or medical condition that may interfere with the absorption distribution, metabolism, or excretion of the study drug
-
A positive urine drug screen or history of regular excessive alcohol consumption or use of tobacco-or nicotine-containing products in excess or from 24-hours prior to admission until discharge
-
Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 halflives preceding the first dose of study med.
-
Out of range blood pressure including current evidence of orthostatic change in blood pressure
-
Abnormal ECG or history or current evidence of clinically important cardiac conduction abnormalities.
-
Also excluded are: pregnant or breastfeeding female subjects; male subjects with partners currently pregnant; male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as described in the protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Clinical Research Unit | Brussels | Belgium | B-1070 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02319148
Other Study ID Numbers:
- A7331022
- 2014-001979-31
First Posted:
Dec 18, 2014
Last Update Posted:
Sep 16, 2016
Last Verified:
Jul 1, 2016
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| 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 |
|---|---|---|---|---|
| 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: First Intervention Period | ||||
| STARTED | 22 | 0 | 0 | 0 |
| COMPLETED | 22 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: First Intervention Period | ||||
| STARTED | 0 | 7 | 7 | 8 |
| COMPLETED | 0 | 6 | 6 | 6 |
| NOT COMPLETED | 0 | 1 | 1 | 2 |
Baseline Characteristics
| 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 |
|---|---|---|---|---|
| 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 Participants | 7 | 7 | 8 | 22 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
38.1
(6.1)
|
33.4
(9.9)
|
35.1
(10.1)
|
35.5
(8.7)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
7
100%
|
7
100%
|
8
100%
|
22
100%
|
Outcome Measures
| Title | Maximum Observed Plasma Concentration (Cmax) of PF-00489791 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)] |
1140
(34)
|
1238
(33)
|
1198
(33)
|
1186
(21)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Itraconazole 200 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 105.28 | |
| Confidence Interval |
(2-Sided) 90% 92.11 to 120.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Diltiazem 240 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 92.54 | |
| Confidence Interval |
(2-Sided) 90% 80.96 to 105.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Verapamil 240 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 116.36 | |
| Confidence Interval |
(2-Sided) 90% 101.86 to 132.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-00489791 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)] |
17880
(36)
|
18140
(24)
|
16840
(20)
|
19560
(30)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Itraconazole 200 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 90.16 | |
| Confidence Interval |
(2-Sided) 90% 78.57 to 103.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Diltiazem 240 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 106.38 | |
| Confidence Interval |
(2-Sided) 90% 92.70 to 122.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Verapamil 240 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 101.71 | |
| Confidence Interval |
(2-Sided) 90% 88.68 to 116.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00489791 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng.hr/mL] |
17580
(36)
|
17980
(24)
|
16760
(20)
|
19400
(30)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Itraconazole 200 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 91.33 | |
| Confidence Interval |
(2-Sided) 90% 79.49 to 104.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Diltiazem 240 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 106.97 | |
| Confidence Interval |
(2-Sided) 90% 93.10 to 122.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PF-00489791 20 mg, PF-00489791 20 mg + Verapamil 240 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of adjusted geometric means |
| Estimated Value | 102.69 | |
| Confidence Interval |
(2-Sided) 90% 89.42 to 117.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00489791 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Median (Full Range) [hour] |
4.00
|
3.50
|
4.00
|
4.00
|
| Title | Apparent Volume of Distribution (Vz/F) of PF-00489791 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [liter] |
18.06
(34)
|
21.65
(18)
|
19.98
(31)
|
19.23
(23)
|
| Title | Apparent Oral Clearance (CL/F) of PF-00489791 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [milliliter per minute (mL/min)] |
18.64
(36)
|
18.37
(24)
|
19.81
(20)
|
17.02
(30)
|
| Title | Terminal Elimination Half-Life (t1/2) of PF-00489791 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Mean (Standard Deviation) [hour] |
11.39
(2.15)
|
13.85
(2.79)
|
11.75
(1.69)
|
13.29
(2.56)
|
| Title | Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Number [participants] |
3
42.9%
|
0
0%
|
0
0%
|
2
9.1%
|
| Title | Number of Participants With Potentially Clinically Significant Vital Signs Findings |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 7 | 7 | 8 |
| Supine SBP <90 mm Hg (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
1
4.5%
|
| Standing SBP <90 mm Hg (n=22,7,6,8) |
0
0%
|
0
0%
|
0
0%
|
1
4.5%
|
| Supine DBP <50 mm Hg (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Standing DBP <50 mm Hg (n=22,7,6,8) |
0
0%
|
0
0%
|
0
0%
|
1
4.5%
|
| Supine Pulse Rate <40 or >120 bpm (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Standing Pulse Rate <40 or >120 bpm (n=22,7,6,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Supine SBP >=30 mm Hg IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Standing SBP >=30 mm Hg IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Supine DBP >=20 mm Hg IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Standing DBP >=20 mm Hg IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Supine SBP >=30 mm Hg DFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Standing SBP >=30 mm Hg DFB (n=22,6,6,7) |
0
0%
|
0
0%
|
1
12.5%
|
1
4.5%
|
| Supine DBP >=20 mm Hg DFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Standing DBP >=20 mm Hg DFB (n=22,6,6,7) |
1
14.3%
|
0
0%
|
1
12.5%
|
1
4.5%
|
| Title | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 7 | 7 | 8 |
| PR Interval >=300 msec (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QRS Complex >=140 msec (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF Interval 450-<480 msec (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF Interval 480-<500 msec (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF Interval >=500 msec (n=22,7,7,8) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR Interval >=25/50% IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QRS Interval >=50% IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTcF Interval 30-<60 msec IFB (n=22,6,6,7) |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
| QTcF Interval >=60 msec IFB (n=22,6,6,7) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Used at Least 1 Concomitant Medication |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 6 | 6 | 6 |
| Drug Treatments |
10
142.9%
|
2
28.6%
|
4
50%
|
2
9.1%
|
| Non-Drug Treatments |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|---|---|
| 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. |
| Measure Participants | 22 | 7 | 7 | 8 | 6 | 6 | 6 |
| AEs |
18
257.1%
|
6
85.7%
|
4
50%
|
3
13.6%
|
6
NaN
|
4
NaN
|
5
NaN
|
| SAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
Adverse Events
| 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 | |||||||
| 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 (%) | # 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
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%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
Other (Not Including 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 | 18/22 (81.8%) | 6/7 (85.7%) | 4/7 (57.1%) | 3/8 (37.5%) | 6/6 (100%) | 4/6 (66.7%) | 5/6 (83.3%) | |||||||
| Cardiac disorders | ||||||||||||||
| Palpitations | 0/22 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal discomfort | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Abdominal distension | 0/22 (0%) | 2/7 (28.6%) | 2/7 (28.6%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Diarrhoea | 0/22 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Dyspepsia | 2/22 (9.1%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Flatulence | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Nausea | 5/22 (22.7%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | |||||||
| Vomiting | 3/22 (13.6%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| General disorders | ||||||||||||||
| Fatigue | 2/22 (9.1%) | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| Investigations | ||||||||||||||
| Alanine aminotransferase increased | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/22 (0%) | 0 | 0/7 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 |
| Back pain | 8/22 (36.4%) | 4/7 (57.1%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Muscle spasms | 4/22 (18.2%) | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Neck pain | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Sensation of heaviness | 2/22 (9.1%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| Myalgia | 3/22 (13.6%) | 1/7 (14.3%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| Nervous system disorders | ||||||||||||||
| Dizziness | 2/22 (9.1%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Head discomfort | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | |||||||
| Headache | 14/22 (63.6%) | 1/7 (14.3%) | 4/7 (57.1%) | 2/8 (25%) | 6/6 (100%) | 4/6 (66.7%) | 2/6 (33.3%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Irritability | 1/22 (4.5%) | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Nocturia | 0/22 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Polyuria | 1/22 (4.5%) | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Spontaneous penile erection | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Rash | 0/22 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Haematoma | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
| Hot flush | 3/22 (13.6%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 5/6 (83.3%) | 2/6 (33.3%) | 1/6 (16.7%) | |||||||
| Orthostatic hypotension | 0/22 (0%) | 0/7 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02319148
Other Study ID Numbers:
- A7331022
- 2014-001979-31
First Posted:
Dec 18, 2014
Last Update Posted:
Sep 16, 2016
Last Verified:
Jul 1, 2016