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| ID | Type | Description | Link |
|---|---|---|---|
| SAD | Other Identifier | Alias Study Number |
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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
This study was previously posted by Pfizer. In March, 2020, sponsorship of the trial was transferred to Biogen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Ascending Dose-1 (Part A) | Experimental | Single ascending doses of BIIB118 administered to healthy volunteers in a cross over study design |
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| Single Ascending Dose-2 (Part A) | Experimental | Single ascending doses of BIIB118 administered to healthy volunteers in a cross over study design |
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| Single Dose Cerebrospinal Fluid (Part B) | Experimental | Single maximum dose from Part A of BIIB118 administered to healthy volunteers to assess the PK of BIIB118 in CSF |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIIB118 | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | 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. | For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
| Number of Participants With Laboratory Abnormalities | 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). | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ). |
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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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New Haven Clinical Research Unit | New Haven | Connecticut | 06511 | United States |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 PF-05251749: Placebo + 30 mg + 250 mg + 500 mg | 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. |
| FG001 | Cohort 1 PF-05251749: 3 mg + Placebo + 250 mg + 500 mg | 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. |
| FG002 | Cohort 1 PF-05251749: 3 mg + 30 mg + Placebo + 500 mg | 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. |
| FG003 | Cohort 1 PF-05251749: 3 mg + 30 mg + 250 mg + Placebo | 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. |
| FG004 | Cohort 2 PF-05251749: Placebo + 100 mg + 500 mg + 1000 mg | 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. |
| FG005 | Cohort 2 PF-05251749: 10 mg + Placebo + 500 mg + 1000 mg | 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. |
| FG006 | Cohort 2 PF-05251749: 10 mg + 100 mg + Placebo + 1000 mg | 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. |
| FG007 | Cohort 2 PF-05251749: 10 mg + 100 mg + 500 mg + Placebo | 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. |
| FG008 | Cohort 3 PF-05251749: 500 mg | 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. |
| FG009 | Cohort 4 PF-05251749: 500 mg Unmilled + 500 mg Milled | 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. |
| FG010 | Cohort 4 PF-05251749: 500 mg Milled + 500 mg Unmilled | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
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| Intervention Period 1 (3 Days) |
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| Intervention Period 2 (3 Days) |
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| Intervention Period 3 (3 Days) |
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| Washout Period 3 (7 Days) |
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| Intervention Period 4 (3 Days) |
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Analysis population was defined as all participants who were randomized.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 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. |
| Units | Counts |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | 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. | Safety analysis set included all participants who received at least 1 dose of study treatment. | Posted | Number | participants | For Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: PF-05251749 3 mg | Participants received a single oral dose of PF-05251749 3 mg oral suspension on Day 1 of Intervention Period in Cohort 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus node dysfunction | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| BIIB118 | Drug | 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 |
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| BIIB118 | Drug | Single dose (Maximum Tolerated Dose) of BIIB118 as extemporaneously prepared solution/suspension |
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| Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
| Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings | 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. | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
| Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2 | 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. | Baseline, Day 1: 2 hours post dose |
| Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2 | 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. | Baseline, Day 1: 6 hours post dose |
| Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2 | 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. | Baseline, Day 3: 48 hours post dose |
| Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2 | 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. | Baseline, Day 1: 2 hours post dose |
| Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2 | 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. | Baseline, Day 1: 48 hours post dose |
| 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 Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749 | 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. | 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 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 | 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. | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
| Apparent Oral Clearance (CL/F) of PF-05251749 | 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. | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
| Apparent Volume of Distribution (Vz/F) of PF-05251749 | 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. | 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 Milled and Unmilled PF-05251749: Cohort 4 | Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast). | 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 Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4 | 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. | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
| 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 | Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast). | Predose, 1.5, 2.5, 4, and 8 hours post dose |
| Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749 | 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. | Predose, 1.5, 2.5, 4, and 8 hours post dose |
| 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 |
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| BG001 | Cohort 2 | 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. |
| BG002 | Cohort 3 | 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. |
| BG003 | Cohort 4 | 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. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| OG001 | Cohort 1: PF-05251749 30 mg | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. |
| OG002 | Cohort 1: PF-05251749 250 mg | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. |
| OG003 | Cohort 1: PF-05251749 500 mg (FED) | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. |
| OG004 | Cohort 2: PF-05251749 10 mg | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| OG005 | Cohort 2: PF-05251749 100 mg | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| OG006 | Cohort 2: PF-05251749 500 mg | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| OG007 | Cohort 2: PF-05251749 1000 mg | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. |
| OG008 | Cohort 1-2: Placebo | 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. |
| OG009 | Cohort 3: PF-05251749 500 mg CSF | 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. |
| OG010 | Cohort 4: PF-05251749 500 mg Unmilled | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. |
| OG011 | Cohort 4: PF-05251749 500 mg Milled | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. |
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| Primary | Number of Participants With Laboratory Abnormalities | 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). | Safety analysis set included all participants who received at least 1 dose of study treatment. | Posted | Number | participants | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
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| Primary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 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. | Safety analysis set included all participants who received at least 1 dose of study treatment. | Posted | Number | participants | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
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| Primary | Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Findings | 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. | Safety analysis set included all participants who received at least 1 dose of study treatment. | Posted | Number | participants | Cohort 1 and 2: Baseline up to Week 8, Cohort 3: Baseline up to Week 2, Cohort 4: Baseline up to Week 3 |
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| Primary | Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 2 Hours Post Dose in Cohorts 1 and 2 | 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. | 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. | Posted | Mean | Standard Deviation | millimeter | Baseline, Day 1: 2 hours post dose |
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| Primary | Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 6 Hours Post Dose in Cohorts 1 and 2 | 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. | 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. | Posted | Mean | Standard Deviation | millimeter | Baseline, Day 1: 6 hours post dose |
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| Primary | Change From Baseline in Bond and Lader Visual Analogue Scale (BL-VAS) at 48 Hours Post Dose in Cohorts 1 and 2 | 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. | 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. | Posted | Mean | Standard Deviation | millimeter | Baseline, Day 3: 48 hours post dose |
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| Primary | Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 2 Hours Post Dose in Cohorts 1 and 2 | 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 1: 2 hours post dose |
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| Primary | Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) at 48 Hours Post Dose in Cohorts 1 and 2 | 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 1: 48 hours post dose |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of PF-05251749 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05251749 | Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast ). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-05251749 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05251749 | 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. | Posted | Median | Full Range | hour | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Plasma Decay Half-Life (t1/2) of PF-05251749 | 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. | 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. | Posted | Mean | Standard Deviation | hour | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Apparent Oral Clearance (CL/F) of PF-05251749 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/hr) | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Apparent Volume of Distribution (Vz/F) of PF-05251749 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Milled and Unmilled PF-05251749: Cohort 4 | Area under the plasma concentration-time profile from time zero to the time of last quantifiable concentration (Clast). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Milled and Unmilled PF-05251749: Cohort 4 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Milled and Unmilled PF-05251749: Cohort 4 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Milled and Unmilled PF-05251749: Cohort 4 | 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. | Posted | Median | Full Range | hour | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose |
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| Secondary | Area Under the Curve From Time Zero to Last Quantifiable Cerebrospinal Fluid (CSF) Concentration (AUClast) of PF-05251749 | Area under the CSF concentration-time profile from time zero to the time of last quantifiable concentration (Clast). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose, 1.5, 2.5, 4, and 8 hours post dose |
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| Secondary | Area Under the Curve From Time Zero to Extrapolated Cerebrospinal Fluid (CSF) Infinite Time [AUC (0 - ∞)] of PF-05251749 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose, 1.5, 2.5, 4, and 8 hours post dose |
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| Secondary | Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Cmax) of PF-05251749 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose, 1.5, 2.5, 4, and 8 hours post dose |
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| Secondary | Time to Reach Maximum Observed Cerebrospinal Fluid (CSF) Concentration (Tmax) of PF-05251749 | 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. | Posted | Median | Full Range | hour | Predose, 1.5, 2.5, 4, and 8 hours post dose |
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| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Cohort 1: PF-05251749 30 mg | Participants received a single oral dose of PF-05251749 30 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | 0 | 6 | 2 | 6 |
| EG002 | Cohort 1: PF-05251749 250 mg | Participants received a single oral dose of PF-05251749 250 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | 0 | 6 | 0 | 6 |
| EG003 | Cohort 1: PF-05251749 500 mg (FED) | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 1. | 0 | 6 | 1 | 6 |
| EG004 | Cohort 2: PF-05251749 10 mg | Participants received a single oral dose of PF-05251749 10 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | 0 | 6 | 0 | 6 |
| EG005 | Cohort 2: PF-05251749 100 mg | Participants received a single oral dose of PF-05251749 100 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | 0 | 6 | 0 | 6 |
| EG006 | Cohort 2: PF-05251749 500 mg | Participants received a single oral dose of PF-05251749 500 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | 0 | 6 | 4 | 6 |
| EG007 | Cohort 2: PF-05251749 1000 mg | Participants received a single oral dose of PF-05251749 1000 mg oral suspension on Day 1 of Intervention Period in Cohort 2. | 0 | 6 | 3 | 6 |
| EG008 | Cohort 1-2: Placebo | 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. | 0 | 15 | 3 | 15 |
| EG009 | Cohort 3: PF-05251749 500 mg CSF | 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. | 0 | 6 | 5 | 6 |
| EG010 | Cohort 4: PF-05251749 500 mg Unmilled | Participants received a single oral dose of PF-05251749 10 mg oral suspension (unmilled) on Day 1 of Intervention Period in Cohort 4. | 0 | 6 | 0 | 6 |
| EG011 | Cohort 4: PF-05251749 500 mg Milled | Participants received a single oral dose of PF-05251749 10 mg oral suspension (milled) on Day 1 of Intervention Period in Cohort 4. | 0 | 6 | 1 | 6 |
| Ventricular extrasystoles | Cardiac disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Catheter site pain | General disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Feeling hot | General disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Hunger | General disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Procedural headache | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 18.1 | Non-systematic Assessment |
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| Blood pressure diastolic decreased | Investigations | MedDRA 18.1 | Non-systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 18.1 | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Non-systematic Assessment |
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| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Non-systematic Assessment |
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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.
| Alertness: Change at 2 hours postdose |
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| Calmness: Baseline |
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| Calmness: Change at 2 hours postdose |
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| Contentment: Baseline |
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| Contentment: Change at 2 hours postdose |
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| Calmness: Change at 6 hours postdose |
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| Contentment: Change at 6 hours postdose |
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| Calmness:Change at 48 hours postdose |
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| Contentment: Change at 48 hours postdose |
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| Parkinsonism: Change at 2 hours postdose |
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| Dystonia: Baseline |
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| Dystonia: Change at 2 hours postdose |
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| Dystonia: 48 hours postdose |
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