Safety, Tolerability and Pharmacokinetics of BIIB118 (PF-05251749)
Sponsor
Biogen (Industry)
Overall Status
Completed
CT.gov ID
NCT02443740
Collaborator
(none)
32
1
3
5
6.4
Study Details
Study Description
Brief Summary
This is a First in human (FIH) single ascending dose study to evaluate the safety, tolerability and pharmacokinetics (PKs) of BIIB118 following single oral doses in healthy human subjects
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This study was previously posted by Pfizer. In March, 2020, sponsorship of the trial was transferred to Biogen.
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
A Phase 1, Randomized, Double Blind, Placebo Controlled Study To Investigate The Safety, Tolerability, Pharmacokinetics And Relative Bioavailability Of Single Escalating Oral Doses Of Pf-05251749 In Healthy Adult Subjects
Actual Study Start Date
:
May 31, 2015
Actual Primary Completion Date
:
Oct 31, 2015
Actual Study Completion Date
:
Oct 31, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single Ascending Dose-1 (Part A) Single ascending doses of BIIB118 administered to healthy volunteers in a cross over study design |
Drug: BIIB118
Single ascending doses of BIIB118 as extemporaneously prepared solution/suspension, once every 2 week in a cross over study: 3 mg, 30 mg, 200 mg, 800 mg and placebo
Other Names:
|
| Experimental: Single Ascending Dose-2 (Part A) Single ascending doses of BIIB118 administered to healthy volunteers in a cross over study design |
Drug: BIIB118
Single ascending doses of BIIB118 as extemporaneously prepared solution/suspension, once every 2 week in a cross over study: 10 mg, 100 mg, 400 mg, and placebo
Other Names:
|
| Experimental: Single Dose Cerebrospinal Fluid (Part B) Single maximum dose from Part A of BIIB118 administered to healthy volunteers to assess the PK of BIIB118 in CSF |
Drug: BIIB118
Single dose (Maximum Tolerated Dose) of BIIB118 as extemporaneously prepared solution/suspension
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3]
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (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.
- Number of Participants With Laboratory Abnormalities [Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3]
Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(<)0.8*lower limit of normal(LLN), MCV,MCH,MCHC,MPV:<0.9*LLN or >1.1*upper limit of normal(ULN), platelet:<0.5*LLN or >1.75*ULN, white blood cell(WBC):<0.6*LLNor>1.5*ULN, lymphocyte,neutrophil,total neutrophil:<0.8*LLN or >1.2*ULN,basophil,eosinophil,monocyte:>1.2*ULN; PTT, PT:>1.1*ULN,Fibrinogen<0.75*ULNor>1.25ULN; total, direct, indirect bilirubin >1.5*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,alkaline phosphatase:> 3.0*ULN,total protein,albumin:<0.8*LLN or >1.2*ULN;blood urea nitrogen,creatinine:>1.3*ULN,uric acid>1.2*ULN;sodium:<0.95*LLN or>1.05*ULN,potassium,chloride, calcium,magnesium,bicarbonate:<0.9*LLN or >1.1*ULN, phosphate<0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN,creatine kinase>2.0*ULN;urine(specific gravity<1.003or>1.030,pH <4.5or>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals>=1,RBC,WBC >=20*ULN,bacteria>20);CSF (WBC>=6,RBC>0,Albumin>35).
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3]
Criteria for clinically significant change from baseline in vital signs: supine systolic blood pressure (SBP) <90 millimeter of mercury (mmHg), supine diastolic BP (DBP) <50 mmHg, supine pulse rate <40 beats per minute (bpm) or >120 bpm. Maximum increase or decrease from baseline in supine SBP greater than or equal to (>=)30 mmHg and maximum increase or decrease from baseline in supine DBP >=20 mmHg.
- Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings [Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3]
ECG parameters included maximum pulse rate (PR) interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for abnormal ECG: Maximum PR interval >=300 milliseconds (msec) or >=25 percent increase when baseline is >200 msec and >=50 percent increase when baseline is less than or equal to (=<) 200 msec; QRS interval >=140 msec or >=50 percent increase from baseline (IFB); and QTcF 30<=change<60 or change>=60 msec increase. The number of participants with abnormal ECG findings are reported.
- Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2 [Baseline, Day 1: 2 hours post dose]
The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) contentment (average of 2 items [total range 0 to 100, where higher scores indicated more contentment]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
- Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2 [Baseline, Day 1: 6 hours post dose]
The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) contentment (average of 2 items [total range 0 to 100, where higher scores indicated more contentment]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
- Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2 [Baseline, Day 3: 48 hours post dose]
The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) contentment (average of 2 items [total range 0 to 100, where higher scores indicated more contentment]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period.
- Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2 [Baseline, Day 1: 2 hours post dose]
ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.
- Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2 [Baseline, Day 1: 48 hours post dose]
ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia.
Secondary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ).
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last*/k el), where C last* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
- Plasma Decay Half-Life (t1/2) of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
Terminal elimination half-life (t1/2). It was calculated as dividing the natural logarithm to the base e (Log e)*2/k el, where k el is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
- Apparent Oral Clearance (CL/F) of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
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.
- Apparent Volume of Distribution (Vz/F) of PF-05251749 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
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.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast).
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last*/k el), where C last* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
- Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4 [Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose]
- Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749 [Predose, 1.5, 2.5, 4, and 8 hours post dose]
Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast).
- Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749 [Predose, 1.5, 2.5, 4, and 8 hours post dose]
AUC (0 -∞) = Area under the CSF concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last*/k el), where C last* was the predicted CSF concentration at the last quantifiable time point estimated from the log-linear regression analysis.
- Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749 [Predose, 1.5, 2.5, 4, and 8 hours post dose]
- Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749 [Predose, 1.5, 2.5, 4, and 8 hours post dose]
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 of non-childbearing potential 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).
Female subjects of non-childbearing potential must meet at least one of the following criteria:
-
Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state;
-
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.
-
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
-
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
-
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion Criteria:
-
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).
-
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).
-
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), repeat per local standard operating procedures (SOP). If orthostatic changes are present and deemed to be clinically significant by the investigator, Subject can be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New Haven Clinical Research Unit | New Haven | Connecticut | United States | 06511 |
Sponsors and Collaborators
- Biogen
Investigators
- Study Director: Medical Director, Biogen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Biogen
ClinicalTrials.gov Identifier:
NCT02443740
Other Study ID Numbers:
- B8001001
- SAD
First Posted:
May 14, 2015
Last Update Posted:
Feb 17, 2021
Last Verified:
Feb 1, 2021
Keywords provided by Biogen
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The study consisted of 4 cohorts. Cohort 1 and 2 was a 4 period crossover sequence of PF-05251749 and matching placebo. Cohort 3 was designed to characterize the pharmacokinetic (PK) of PF-05251749 in cerebrospinal fluid (CSF) samples. Cohort 4 was a 2 period crossover sequence of unmilled and milled PF-05251749. |
| Arm/Group Title | Cohort 1 PF-05251749: Placebo + 30 mg + 250 mg + 500 mg | Cohort 1 PF-05251749: 3 mg + Placebo + 250 mg + 500 mg | Cohort 1 PF-05251749: 3 mg + 30 mg + Placebo + 500 mg | Cohort 1 PF-05251749: 3 mg + 30 mg + 250 mg + Placebo | Cohort 2 PF-05251749: Placebo + 100 mg + 500 mg + 1000 mg | Cohort 2 PF-05251749: 10 mg + Placebo + 500 mg + 1000 mg | Cohort 2 PF-05251749: 10 mg + 100 mg + Placebo + 1000 mg | Cohort 2 PF-05251749: 10 mg + 100 mg + 500 mg + Placebo | Cohort 3 PF-05251749: 500 mg | Cohort 4 PF-05251749: 500 mg Unmilled + 500 mg Milled | Cohort 4 PF-05251749: 500 mg Milled + 500 mg Unmilled |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: Placebo, PF-05251749 30 milligram (mg), 250 mg and 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, placebo, PF-05251749 250 mg and 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, 30 mg, placebo and PF-05251749 500 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 3 mg, 30 mg, 250 mg and placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 placebo, PF-05251749 100 mg, PF-05251749 500 mg, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 placebo, PF-05251749 500 mg, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 100 mg, PF-05251749 placebo, PF-05251749 1000 mg in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 10 mg, PF-05251749 100 mg, PF-05251749 500 mg, PF-05251749 placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 500 mg suspension on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500mg unmilled, PF-05251749 500mg milled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500 mg milled, PF-05251749 500 mg unmilled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 2 | 2 | 2 | 3 | 2 | 4 | 3 | 2 | 6 | 3 | 3 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 6 | 3 | 3 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 3 | 3 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 3 | 3 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Intervention Period 1 (3 Days) | |||||||||||
| STARTED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| COMPLETED | 1 | 2 | 2 | 3 | 2 | 2 | 2 | 2 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: Placebo, PF-05251749 30 mg, 250 mg and 500 mg; PF-05251749 3 mg, placebo, PF-05251749 250 mg and 500 mg; PF-05251749 3 mg, 30 mg, placebo and PF-05251749 500 mg; PF-05251749 3 mg, 30 mg, 250 mg and placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state except PF-05251749 500 mg. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (4 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 placebo, PF-05251749 100mg, PF-05251749 500mg, PF-05251749 1000mg; PF-05251749 10mg, PF-05251749 placebo, PF-05251749 500mg, PF-05251749 1000mg; PF-05251749 10mg, PF-05251749 100mg, PF-05251749 placebo, PF-05251749 1000mg and PF-05251749 10mg, PF-05251749 100mg, PF-05251749 500mg, PF-05251749 placebo in Intervention Period 1, 2, 3 and 4 respectively. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Participants received a single oral dose of PF-05251749 500 mg suspension on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 suspension on Day 1 of each Intervention Period (2 Intervention Periods of 3 days each). Participants received study treatment in following sequences: PF-05251749 500mg unmilled, PF-05251749 500mg milled and PF-05251749 500mg milled, PF-05251749 500mg unmilled in Intervention Period 1 and 2. All doses were administered in fasted state. A washout period of at least 7 days was maintained between each Intervention Period. | Total of all reporting groups |
| Overall Participants | 9 | 11 | 6 | 6 | 32 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
32.7
(10.2)
|
41.3
(6.3)
|
44.5
(6.0)
|
38.5
(11.2)
|
38.9
(9.2)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
9
100%
|
11
100%
|
6
100%
|
6
100%
|
32
100%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
|---|---|
| Description | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious adverse event (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. |
| Time Frame | For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 | 6 | 6 | 6 |
| Number [participants] |
0
0%
|
2
18.2%
|
0
0%
|
1
16.7%
|
0
0%
|
0
NaN
|
4
NaN
|
3
NaN
|
3
NaN
|
5
NaN
|
0
NaN
|
1
NaN
|
| Title | Number of Participants With Laboratory Abnormalities |
|---|---|
| Description | Hemoglobin(Hgb),hematocrit,red blood cell(RBC):less than(<)0.8*lower limit of normal(LLN), MCV,MCH,MCHC,MPV:<0.9*LLN or >1.1*upper limit of normal(ULN), platelet:<0.5*LLN or >1.75*ULN, white blood cell(WBC):<0.6*LLNor>1.5*ULN, lymphocyte,neutrophil,total neutrophil:<0.8*LLN or >1.2*ULN,basophil,eosinophil,monocyte:>1.2*ULN; PTT, PT:>1.1*ULN,Fibrinogen<0.75*ULNor>1.25ULN; total, direct, indirect bilirubin >1.5*ULN,aspartate aminotransferase,alanine aminotransferase,gamma-glutamyl transferase,alkaline phosphatase:> 3.0*ULN,total protein,albumin:<0.8*LLN or >1.2*ULN;blood urea nitrogen,creatinine:>1.3*ULN,uric acid>1.2*ULN;sodium:<0.95*LLN or>1.05*ULN,potassium,chloride, calcium,magnesium,bicarbonate:<0.9*LLN or >1.1*ULN, phosphate<0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN,creatine kinase>2.0*ULN;urine(specific gravity<1.003or>1.030,pH <4.5or>8,glucose,ketone,protein,blood/Hgb,bilirubin,leukocyte esterase,crystals>=1,RBC,WBC >=20*ULN,bacteria>20);CSF (WBC>=6,RBC>0,Albumin>35). |
| Time Frame | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 | 6 | 6 | 6 |
| Number [participants] |
3
33.3%
|
2
18.2%
|
1
16.7%
|
2
33.3%
|
3
9.4%
|
3
NaN
|
4
NaN
|
3
NaN
|
6
NaN
|
5
NaN
|
1
NaN
|
0
NaN
|
| Title | Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
|---|---|
| Description | Criteria for clinically significant change from baseline in vital signs: supine systolic blood pressure (SBP) <90 millimeter of mercury (mmHg), supine diastolic BP (DBP) <50 mmHg, supine pulse rate <40 beats per minute (bpm) or >120 bpm. Maximum increase or decrease from baseline in supine SBP greater than or equal to (>=)30 mmHg and maximum increase or decrease from baseline in supine DBP >=20 mmHg. |
| Time Frame | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 | 6 | 6 | 6 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings |
|---|---|
| Description | ECG parameters included maximum pulse rate (PR) interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for abnormal ECG: Maximum PR interval >=300 milliseconds (msec) or >=25 percent increase when baseline is >200 msec and >=50 percent increase when baseline is less than or equal to (=<) 200 msec; QRS interval >=140 msec or >=50 percent increase from baseline (IFB); and QTcF 30<=change<60 or change>=60 msec increase. The number of participants with abnormal ECG findings are reported. |
| Time Frame | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 | 6 | 6 | 6 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
NaN
|
3
NaN
|
2
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Title | Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2 |
|---|---|
| Description | The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) contentment (average of 2 items [total range 0 to 100, where higher scores indicated more contentment]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period. |
| Time Frame | Baseline, Day 1: 2 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 |
| Alertness: Baseline |
63.95
(21.656)
|
83.05
(9.176)
|
79.12
(21.139)
|
74.92
(24.371)
|
82.22
(14.773)
|
89.98
(7.900)
|
81.37
(22.535)
|
87.57
(19.500)
|
83.47
(14.945)
|
| Alertness: Change at 2 hours postdose |
11.48
(15.395)
|
8.87
(20.227)
|
8.65
(15.615)
|
14.62
(23.859)
|
2.28
(7.327)
|
4.17
(3.247)
|
0.30
(9.562)
|
-3.40
(10.744)
|
7.45
(18.622)
|
| Calmness: Baseline |
68.83
(27.518)
|
82.83
(10.424)
|
84.67
(13.227)
|
70.83
(23.962)
|
73.58
(19.135)
|
79.92
(21.280)
|
90.33
(11.206)
|
82.83
(19.372)
|
80.10
(23.051)
|
| Calmness: Change at 2 hours postdose |
9.08
(14.857)
|
12.42
(25.305)
|
5.08
(5.800)
|
2.33
(26.174)
|
8.75
(6.594)
|
5.42
(5.545)
|
3.33
(7.878)
|
-10.33
(33.673)
|
8.30
(25.787)
|
| Contentment: Baseline |
68.10
(26.737)
|
83.20
(11.331)
|
84.83
(11.542)
|
78.03
(18.151)
|
85.00
(14.105)
|
84.63
(18.600)
|
90.50
(9.294)
|
89.70
(15.592)
|
86.09
(16.013)
|
| Contentment: Change at 2 hours postdose |
7.57
(14.995)
|
8.20
(21.017)
|
5.20
(15.491)
|
7.40
(29.055)
|
4.90
(4.688)
|
1.80
(5.362)
|
-0.43
(8.584)
|
-0.97
(11.598)
|
5.55
(20.253)
|
| Title | Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2 |
|---|---|
| Description | The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) contentment (average of 2 items [total range 0 to 100, where higher scores indicated more contentment]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period. |
| Time Frame | Baseline, Day 1: 6 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 |
| Alertness: Change at 6 hours postdose |
9.25
(22.935)
|
16.85
(16.053)
|
12.72
(15.116)
|
18.72
(22.991)
|
3.43
(6.825)
|
-2.50
(18.228)
|
-1.07
(10.708)
|
-1.00
(8.820)
|
5.93
(25.464)
|
| Calmness: Change at 6 hours postdose |
6.67
(7.916)
|
6.83
(16.549)
|
-0.67
(16.136)
|
16.00
(13.936)
|
2.58
(6.829)
|
8.33
(8.542)
|
-1.58
(16.209)
|
2.17
(2.658)
|
8.83
(25.441)
|
| Contentment: Change at 6 hours postdose |
7.53
(17.418)
|
11.60
(19.555)
|
4.80
(9.728)
|
12.20
(23.074)
|
1.20
(4.746)
|
0.80
(9.955)
|
0.40
(6.331)
|
3.03
(9.063)
|
7.51
(19.539)
|
| Title | Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2 |
|---|---|
| Description | The BL-VAS monitored the subjective mood of each participant on 16 mood scales. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered (example, alert/drowsy; calm/excited; content/tensed). The individual responses from the 16 mood scales were then combined to make three affective dimensions/subscales a) alertness (average of 9 items [total range 0 to 100, where each item is ordered so that higher scores indicated more alertness]), b) contentment (average of 2 items [total range 0 to 100, where higher scores indicated more contentment]), and c) calmness (average of 5 items [total range 0 to 100, where higher scores indicated more calmness]). Baseline is defined as the last available recording prior to dosing on Day 1 of the first Period. |
| Time Frame | Baseline, Day 3: 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 |
| Alertness: Change at 48 hours postdose |
15.83
(15.371)
|
11.45
(13.703)
|
15.80
(14.284)
|
20.92
(19.343)
|
3.90
(13.966)
|
6.08
(7.372)
|
6.12
(6.228)
|
5.62
(6.576)
|
9.67
(12.048)
|
| Calmness:Change at 48 hours postdose |
-0.50
(23.791)
|
6.17
(26.470)
|
5.33
(9.983)
|
8.67
(23.920)
|
3.00
(5.550)
|
-4.83
(20.966)
|
-11.75
(25.284)
|
10.00
(18.213)
|
5.27
(18.547)
|
| Contentment: Change at 48 hours postdose |
13.70
(17.876)
|
10.77
(16.112)
|
6.87
(19.681)
|
19.60
(21.045)
|
4.00
(2.343)
|
2.87
(3.090)
|
4.60
(7.859)
|
4.97
(5.967)
|
7.56
(11.916)
|
| Title | Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2 |
|---|---|
| Description | ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia. |
| Time Frame | Baseline, Day 1: 2 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 |
| Parkinsonism: Baseline |
0.0
(0.00)
|
0.3
(0.52)
|
0.3
(0.52)
|
0.3
(0.52)
|
0.2
(0.41)
|
0.0
(0.00)
|
0.2
(0.41)
|
0.2
(0.41)
|
0.1
(0.35)
|
| Parkinsonism: Change at 2 hours postdose |
0.0
(0.00)
|
0.2
(0.75)
|
-0.3
(0.52)
|
-0.3
(0.52)
|
0.2
(0.41)
|
0.0
(0.00)
|
-0.2
(0.41)
|
-0.2
(0.41)
|
0.0
(0.38)
|
| Dystonia: Baseline |
0.0
(0.00)
|
0.2
(0.41)
|
0.2
(0.41)
|
0.2
(0.41)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.1
(0.26)
|
| Dystonia: Change at 2 hours postdose |
0.0
(0.00)
|
0.0
(0.00)
|
-0.2
(0.41)
|
-0.2
(0.41)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
| Title | Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2 |
|---|---|
| Description | ESRS is a clinician rated scale to assess parkinsonism,dystonia,dyskinesia,akathisia.The ESRS consists of 4 subscales and 4 clinicians global impressions-severity scales(CGI-S scales):I)a questionnaire of extrapyramidal symptoms or drug-induced movement disorders(a series of 4-point Likert scale questions with 0=Absent and 3=Severe);II)an examination of Parkinsonism and akathisia(7-point Likert scale with 0=Absent,6=extremely severe);III)an examination of dystonia(7-point Likert scale with 0=Absent,6=extremely severe);IV)an examination of dyskinesia(7-point Likert scale with 0=normal,6=most severe);V)toVIII)CGI-S scales(9-point Likert scale with 0=Absent,8=extremely severe)of tardive dyskinesia,parkinsonism,dystonia,akathisia.ESRS-Parkinsonism:total score range:0 to 14 where higher scores indicates greater severity;ESRS-dystonia:total score range:0 to 14 where higher scores indicates greater severity.Change from baseline was only observed in examination of parkinsonism and dystonia. |
| Time Frame | Baseline, Day 1: 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome measure was not planned to be analyzed in Cohort 3 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 15 |
| Parkinsonism:48 hours postdose |
0.0
(0.00)
|
0.0
(0.63)
|
0.0
(0.63)
|
-0.2
(0.41)
|
0.2
(0.41)
|
0.0
(0.00)
|
-0.2
(0.41)
|
-0.2
(0.41)
|
-0.1
(0.26)
|
| Dystonia: 48 hours postdose |
0.0
(0.00)
|
-0.2
(0.41)
|
-0.2
(0.41)
|
-0.2
(0.41)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
0.0
(0.00)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of PF-05251749 |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)] |
16.7
(38)
|
173.9
(33)
|
1725
(39)
|
1218
(33)
|
60.08
(12)
|
893.6
(32)
|
3078
(18)
|
4582
(35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 500 mg (FED), Cohort 2: PF-05251749 500 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio. |
| Estimated Value | 39.58 | |
| Confidence Interval |
(2-Sided) 90% 30.14 to 51.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values have been back-transformed from the log scale. | |
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749 |
|---|---|
| Description | Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ). |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)] |
58.95
(52)
|
714.7
(48)
|
6542
(46)
|
14120
(35)
|
281.9
(19)
|
3548
(27)
|
17520
(23)
|
33420
(36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 500 mg (FED), Cohort 2: PF-05251749 500 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio |
| Estimated Value | 80.60 | |
| Confidence Interval |
(2-Sided) 90% 59.74 to 108.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values have been back-transformed from the log scale. | |
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749 |
|---|---|
| Description | AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last*/k el), where C last* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
67.62
(50)
|
729.2
(48)
|
6607
(47)
|
14350
(35)
|
300.8
(19)
|
3623
(27)
|
17910
(24)
|
33990
(36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 500 mg (FED), Cohort 2: PF-05251749 500 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio |
| Estimated Value | 80.12 | |
| Confidence Interval |
(2-Sided) 90% 58.92 to 108.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values have been back-transformed from the log scale. | |
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749 |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK concentration analysis set included all enrolled participants who were treated and had at least 1 measurable concentration in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Median (Full Range) [hour] |
1.00
|
1.00
|
1.00
|
3.00
|
1.00
|
1.00
|
1.25
|
1.00
|
| Title | Plasma Decay Half-Life (t1/2) of PF-05251749 |
|---|---|
| Description | Terminal elimination half-life (t1/2). It was calculated as dividing the natural logarithm to the base e (Log e)*2/k el, where k el is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [hour] |
5.255
(2.5047)
|
8.563
(3.3747)
|
7.707
(2.3957)
|
8.400
(1.1415)
|
8.863
(2.2617)
|
9.520
(2.6104)
|
9.513
(2.1843)
|
8.888
(1.2778)
|
| Title | Apparent Oral Clearance (CL/F) of PF-05251749 |
|---|---|
| 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 | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/hr)] |
44.38
(50)
|
41.18
(48)
|
37.87
(47)
|
34.87
(35)
|
33.25
(19)
|
27.60
(27)
|
27.90
(24)
|
29.45
(36)
|
| Title | Apparent Volume of Distribution (Vz/F) of PF-05251749 |
|---|---|
| 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 | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. |
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Liter] |
298.9
(37)
|
458.5
(37)
|
396.7
(29)
|
419.0
(34)
|
415.1
(22)
|
365.7
(31)
|
373.7
(18)
|
374.4
(42)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4 |
|---|---|
| Description | Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast). |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol. |
| Arm/Group Title | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
12600
(22)
|
19210
(17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 3 mg, Cohort 1: PF-05251749 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio |
| Estimated Value | 65.58 | |
| Confidence Interval |
(2-Sided) 90% 62.18 to 69.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values have been back-transformed from the log scale. | |
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4 |
|---|---|
| Description | AUC (0 -∞) = Area under the plasma concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last*/k el), where C last* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol. |
| Arm/Group Title | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
13440
(27)
|
19590
(19)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 3 mg, Cohort 1: PF-05251749 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio |
| Estimated Value | 68.62 | |
| Confidence Interval |
(2-Sided) 90% 63.27 to 74.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values have been back-transformed from the log scale. | |
| Title | Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4 |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol. |
| Arm/Group Title | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
1007
(18)
|
3385
(11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 3 mg, Cohort 1: PF-05251749 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio. |
| Estimated Value | 29.76 | |
| Confidence Interval |
(2-Sided) 90% 24.17 to 36.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values have been back-transformed from the log scale. | |
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4 |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 3, as pre-specified in protocol. |
| Arm/Group Title | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled |
|---|---|---|
| Arm/Group Description | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
| Measure Participants | 6 | 6 |
| Median (Full Range) [hour] |
2.50
|
1.00
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749 |
|---|---|
| Description | Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast). |
| Time Frame | Predose, 1.5, 2.5, 4, and 8 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) | Cohort 3: PF-05251749 500 mg CSF |
|---|---|---|
| Arm/Group Description | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
1824
(31)
|
10920
(28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 3 mg, Cohort 1: PF-05251749 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio |
| Estimated Value | 16.71 | |
| Confidence Interval |
(2-Sided) 90% 15.35 to 18.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values were back-transformed from the log scale. | |
| Title | Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749 |
|---|---|
| Description | AUC (0 -∞) = Area under the CSF concentration- time profile from time zero extrapolated to infinite time. It was calculated as AUC last + (C last*/k el), where C last* was the predicted CSF concentration at the last quantifiable time point estimated from the log-linear regression analysis. |
| Time Frame | Predose, 1.5, 2.5, 4, and 8 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) | Cohort 3: PF-05251749 500 mg CSF |
|---|---|---|
| Arm/Group Description | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
NA
(NA)
|
NA
(NA)
|
| Title | Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749 |
|---|---|
| Description | |
| Time Frame | Predose, 1.5, 2.5, 4, and 8 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) | Cohort 3: PF-05251749 500 mg CSF |
|---|---|---|
| Arm/Group Description | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
354.6
(31)
|
2331
(29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: PF-05251749 3 mg, Cohort 1: PF-05251749 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Geometric Mean Ratio |
| Estimated Value | 15.21 | |
| Confidence Interval |
(2-Sided) 90% 13.29 to 17.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Values were back-transformed from the log scale. | |
| Title | Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749 |
|---|---|
| Description | |
| Time Frame | Predose, 1.5, 2.5, 4, and 8 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all enrolled participants who were treated and had at least 1 measurable PK parameter of interest in at least 1 treatment period. This outcome measure was not planned to be analyzed for Cohort 1, 2 and 4, as pre-specified in protocol. |
| Arm/Group Title | Cohort 3: PF-05251749 500 mg (Plasma CSF Concentration) | Cohort 3: PF-05251749 500 mg CSF |
|---|---|---|
| Arm/Group Description | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. |
| Measure Participants | 6 | 6 |
| Median (Full Range) [hour] |
1.59
|
1.37
|
Adverse Events
| Time Frame | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||
| Arm/Group Title | Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled | ||||||||||||
| Arm/Group Description | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | Participants received a single oral dose of placebo matching to PF-05251749 oral suspension on Day 1 of Intervention Period in Cohort 1 and 2. | Participants received a single oral suspension of PF-05251749 500 mg on Day 1. CSF samples were collected for a total of 10 hours beginning 2 hours predose and 8 hours post dose. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
| Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled | |||||||||||||
| 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 | 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) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||
| Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled | |||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||
| Cohort 1: PF-05251749 3 mg | Cohort 1: PF-05251749 30 mg | Cohort 1: PF-05251749 250 mg | Cohort 1: PF-05251749 500 mg (FED) | Cohort 2: PF-05251749 10 mg | Cohort 2: PF-05251749 100 mg | Cohort 2: PF-05251749 500 mg | Cohort 2: PF-05251749 1000 mg | Cohort 1-2: Placebo | Cohort 3: PF-05251749 500 mg CSF | Cohort 4: PF-05251749 500 mg Unmilled | Cohort 4: PF-05251749 500 mg Milled | |||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) | 3/6 (50%) | 3/15 (20%) | 5/6 (83.3%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||
| Sinus node dysfunction | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/15 (6.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Ventricular extrasystoles | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/15 (6.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Diarrhoea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 1/15 (6.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Flatulence | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Nausea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/15 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Vomiting | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| General disorders | ||||||||||||||||||||||||
| Catheter site pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Feeling hot | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Hunger | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Vessel puncture site bruise | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Vessel puncture site pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/15 (6.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Infections and infestations | ||||||||||||||||||||||||
| Upper respiratory tract infection | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Contusion | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||||||
| Post lumbar puncture syndrome | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Procedural headache | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 3/6 (50%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Procedural pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Investigations | ||||||||||||||||||||||||
| Blood pressure diastolic decreased | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Electrocardiogram QT prolonged | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Flank pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Musculoskeletal stiffness | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 3/6 (50%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||
| Dizziness | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Headache | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||
| Anxiety | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Sleep apnoea syndrome | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/15 (6.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Cold sweat | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||||||||||
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:
Biogen
ClinicalTrials.gov Identifier:
NCT02443740
Other Study ID Numbers:
- B8001001
- SAD
First Posted:
May 14, 2015
Last Update Posted:
Feb 17, 2021
Last Verified:
Feb 1, 2021