Phase 1
Completed N=46
Clinical Trial In Healthy Volunteers And Health Elderly Volunteers To Evaluate The Safety, Tolerability And Blood Concentration After Single And Multiple Escalating Oral Doses Of PF-06751979.
Healthy Subjects
Source: ClinicalTrials.gov NCT02793232 ↗
Enrolled (actual)
46
Serious AEs
0.0%
Results posted
Sep 2018
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) — 1; 3; 2; 6 participants
Summary
This study will test the safety, tolerability and blood concentrations of single and multiple oral doses of PF-06751979 in health subjects and healthy elderly subjects. PF-06751979 is being developed for the treatment of Alzheimer's disease.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
1; 3; 2; 6; 4; 6 | — |
| PRIMARY Number of Participants With Abnormal Physical Examinations Findings |
1; 5; 0; 0; 0; 6 | — |
| PRIMARY Number of Participants With Abnormal Neurological Examinations Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline |
0; 0; 0; 0; 0 | — |
| PRIMARY Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7 |
0; 0; 0; 0; 0 | — |
| PRIMARY Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 |
0; 0; 0; 0; 0 | — |
| PRIMARY Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19 |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Vital Sign Abnormalities |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities |
6; 5; 2; 3; 5; 5 | — |
| SECONDARY Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 |
643.2; 1436; 1829; 630.2 | — |
| SECONDARY Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 |
20500; 41710; 58190; 20170 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 |
22850; 44980; 63420; 23260 | — |
| SECONDARY Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 |
3.218; 3.592; 3.387; 3.154 | — |
| SECONDARY Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979 |
102.6; 104.2; 107.9; 100.9 | — |
| SECONDARY Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979 |
114.1; 112.4; 117.6; 116.4 | — |
| SECONDARY Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 |
4.00; 3.02; 3.01; 6.00 | — |
| SECONDARY Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 |
35.20; 34.70; 35.85; 33.38 | — |
| SECONDARY Part A: Apparent Clearance (CL/F) of PF-06751979 |
145.8; 148.3; 142.0; 143.3 | — |
| SECONDARY Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 |
433.7; 433.0; 431.1; 408.1 | — |
| SECONDARY Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 |
442.7; 983.2; 818.7; 2000; 837.6; 1869 | — |
| SECONDARY Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 |
6380; 13260; 13810; 31210; 13990; 29470 | — |
| SECONDARY Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 |
4.00; 4.00; 3.00; 2.00; 4.00; 4.00 | — |
| SECONDARY Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 |
3.541; 3.576; 6.549; 7.272; 6.702; 6.794 | — |
| SECONDARY Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 |
51.04; 48.21; 110.4; 113.5; 111.8; 107.1 | — |
| SECONDARY Part B: Apparent Clearance (CL/F) of PF-06751979 |
151.0; 146.9; 149.0; 155.3 | — |
| SECONDARY Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 |
388.4; 857.3; 390.3; 868.5 | — |
| SECONDARY Part B: Peak-to-Trough Ratio of PF-06751979 |
2.111; 2.332; 2.145; 2.151 | — |
| SECONDARY Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 |
2.165; 2.355; 2.190; 2.265 | — |
| SECONDARY Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 |
1.849; 2.033; 1.892; 1.923 | — |
| SECONDARY Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 |
30.73; 37.79 | — |
| SECONDARY Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 |
390.5; 498.3 | — |
| SECONDARY Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 |
377.1; 879.4 | — |
| SECONDARY Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 |
5238; 14750 | — |
| SECONDARY Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 |
4.00; 4.00 | — |
| SECONDARY Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 |
3.019; 7.035 | — |
| SECONDARY Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 |
41.93; 118.0 | — |
| SECONDARY Part C: Apparent Oral Clearance (CL/F) |
141.4 | — |
| SECONDARY Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 |
429.9 | — |
| SECONDARY Part C: Peak-to-Trough Ratio of PF-06751979 |
2.045 | — |
| SECONDARY Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 |
2.814 | — |
| SECONDARY Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 |
2.332 | — |
| SECONDARY Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 |
40.76 | — |
| SECONDARY Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 |
496.1 | — |
| SECONDARY Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) |
12.93; 25.93 | — |
| SECONDARY Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) |
10.36; 9.429 | — |
| SECONDARY Part B: Renal Clearance of PF-06751979 |
15.54; 14.68 | — |
| SECONDARY Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments |
-4.223; -80.324; -87.935; -10.031; -85.452; -92.927 | <0.0001 sig |
Eligibility Criteria
Inclusion Criteria
- Healthy female subjects of non childbearing potential and male subjects.
- Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 (32 kg/m2 for healthy elderly); and a total body weight >50 kg (110 lbs) at Screening.
- Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study.
- Additional criterion for subjects of Japanese descent who may be enrolled in Part B (multiple ascending dose cohorts in healthy subjects): Japanese subjects who have four Japanese grandparents born in Japan.
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 the time of dosing).
- Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
- Unwilling or unable to comply with the Lifestyle Guidelines described in the protocol.
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
- Any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
Data sourced from ClinicalTrials.gov (NCT02793232). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.