Healthy Adult Subjects and Healthy Elderly SubjectsPhase 1NCT02440100
A Phase 1 Study To Characterize The Safety, Tolerability, PK And PK Of Repeat Doses Of PF-06648671 In Healthy Adults And Healthy Elderly Subjects
A Phase 1 study testing PF-06648671 and Midazolam in people with Healthy Adult Subjects and Healthy Elderly Subjects, run by Pfizer at 1 site in Belgium.
Trial summary
This is an investigator-and-subject blind, phase 1 study to characterize the safety, tolerability, pharmacokinetics and central and peripheral pharmacodynamics of 14-day repeated ascending doses of PF-06648671 once a day in healthy adults (part 1) and repeated doses at the maximum tolerated dose (MTD) defined in part… Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Subjects and Healthy Elderly Subjects
- What is being tested?
- PF-06648671 and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteBelgium
- Study dates
- May 2015to Oct 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:
- For Part 1 and Part 3 specific: Healthy female subjects of non childbearing potential and male subjects who, at the time of screening, are 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).
- For Part 2 specific: Female subjects of non childbearing potential and male subjects who, at the time of screening, are between the age of 65 and 85 years, inclusive. Subjects must be in good health as determined by the Investigator based on a detailed medical history, full physical examination (including blood pressure and pulse rate measurement), 12 lead ECG and clinical laboratory tests. Subjects with mild, chronic, stable disease eg, controlled hypertension, non insulin dependent diabetes, osteoarthritis may be enrolled if deemed medically prudent by the investigator. Subjects taking daily prescription or non prescription medications for management of acceptable chronic medical conditions must be on a stable dose of these, as defined by non change in dose for the 3 months prior to the first dose of study medication and no planned changes during the conduct of the study.
- 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; status may be confirmed by having a serum follicle stimulating hormone (FSH) level confirming the post menopausal state;
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
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- Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations 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).
- For Part 2 specific: the creatinine clearance greater than 60 mL/min using the Cockcroft Gault method.
- 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.
Who cannot join
- For Part 1 and Part 3 specific: 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) at the discretion of the investigator.
- For Part 2 specific: Recent (eg, last 6 months) evidence or history of unstable disease or moderate to severe conditions which would, in the Investigator's opinion, interfere with the study evaluations or impact on the safety of participating subjects including but not limited to anemia, liver disease, stroke.
- Any condition possibly affecting drug absorption (eg, gastrectomy).
- A positive urine drug screen.
- History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
- 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.
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- Screening supine blood pressure ≥140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is ≥ 140 mm Hg (systolic) or 90 mm Hg (diastolic), the BP should be repeated two more times, following 2 minutes rest and the average of the three BP values should be used to determine the subject's eligibility.
- Screening supine12 lead ECG demonstrating QTcf >450 or a QRS interval >120 msec. If QTcf exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
- Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transminase (SGPT) 1.5x upper limit of normal (ULN);
- Total bilirubin 1.5 x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ULN.
- 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 or longer based upon the compound's half life characteristics.
- For Part 1 and Part 3 specific: Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of ≤ 1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case by case basis following approval by the sponsor.
- For Part 2 specific: Systemic therapy with any of the following cytochrome P450 (CYP) 3A4 strong and moderate inhibitors/inducers within 7 days or 5 half lives (whichever was longer) prior to the first dose of study medication, or during the study: phenobarbital, carbamazepine, phenytoin, rifampin, rifabutin, St. John's Wort, bosentan, modafinil, nafcillin, aprepitant, ciprofloxacin, boceprevir, clarithromycin, conivaptan, grapefruit juice, itraconazole, ketoconazole, mibefradil, nefazodone, posaconazole, telaprevir, telithromycin, voriconazole, aprepitant, diltiazem, erythromycin, fluconazole, verapamil and human immunodeficiency virus (HIV) protease inhibitors (eg, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, fosamprenavir, etc).
- For Part 2 specific: sensitive CYP3A substrates or CYP3A substrates with narrow therapeutic index within 7 days or 5 half lives (whichever was longer) prior to the first dose of study medication, or during the study. However, this exclusion may be removed if the Part 1 results suggest low risk.
- Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication.
- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
- History of sensitivity to heparin or heparin induced thrombocytopenia.
- Unwilling or unable to comply with the Lifestyle Guidelines described in this 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.
- Other 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.
- For Cohorts 3 5 in Part 1 specific: Subjects with a history of significant active bleeding, coagulation disorder or clinically significant finding on PT/PTT/INR at Screening.
- For Cohorts 3 5 in Part 1 specific: Subjects with lower spinal malformations (on physical examination or lumber X ray), local spinal/skin infection, or other abnormalities that would exclude puncture (LP).
- For Cohorts 3 5 in Part 1 specific: Subjects with allergy to lidocaine or its derivative.
- Use of tobacco or nicotine containing products in excess of the equivalent of 5 cigarettes per day.
- Subjects who answer "Yes" to the Columbia Suicide Severity Rating Scale (C SSRS) questions 4 or 5. In addition, subjects deemed by the investigator to be at significant risk of suicidal or violent behavior should be excluded.
- Subjects who have attempted suicide in the past.
- Subjects who have unexplained history of sudden death in their family.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Investigator-and-subject Blind, Phase 1 Study To Characterize The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Repeat Doses Of Pf-06648671 In Healthy Adult Subjects And Healthy Elderly Subjects
This is an investigator-and-subject blind, phase 1 study to characterize the safety, tolerability, pharmacokinetics and central and peripheral pharmacodynamics of 14-day repeated ascending doses of PF-06648671 once a day in healthy adults (part 1) and repeated doses at the maximum tolerated dose (MTD) defined in part 1 in healthy elderly subjects (part 2). The study also include an optional cohort (part 3) to evaluate the drug interaction between PF-06648671 at MTD and CYP3A probe, midazolam
- Being tested
- PF-06648671, Midazolam, Placebo
- Keywords
- Phase 1, Multiple doses of PF-06648671, safety, tolerability, PK, plasma and CSF abeta, drug interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06648671Drug
experimental Pfizer compound which will be dosed as oral suspension, once a day for 14 days
MidazolamDrug
commercial available oral solution of 2 mg midazolam as CYP3A probe substrate for drug interaction evaluation. Midazolam will be given as single dose with and without co-administration of PF-06648671
PlaceboDrug
Matching placebo which will be given as oral suspension, once a day for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Multiple Doses PF-06648671 (Cohort1) | Experimental | Healthy subjects receive 14-day repeated dose once a day at 4 mg of PF-06648671 or matching placebo Receives: Drug: PF-06648671; Drug: Placebo |
| Multiple Doses PF-06648671 (cohort 2) | Experimental | Healthy subject receive 14-day repeated dose once a day at 12 mg of PF-06648671 or matching placebo Receives: Drug: PF-06648671; Drug: Placebo |
| Multiple doses PF-06648671 (cohort 3) | Experimental | Healthy subject receive 14-day repeated dose once a day at 40 mg of PF-06648671 or matching placebo and CSF LP is collected at baseline and steady state predose on day 1 and 14 Receives: Drug: PF-06648671; Drug: Placebo |
| Multiple Doses PF-06648671 (cohort 4) | Experimental | Healthy subject receive 14-day repeated dose once a day at 40 mg of PF-06648671 or matching placebo Receives: Drug: PF-06648671; Drug: Placebo |
| Multiple Doses PF-06648671 (cohort 5) | Experimental | Healthy subject receive 14-day repeated dose once a day at 100 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 15, 24 hours after last dosing on day 14 Receives: Drug: PF-06648671; Drug: Placebo |
| Multiple Doses in Healthy Elderly (cohort 7) | Experimental | Healthy Elderly subjects receive 14-day repeated dose once a day at MTD PF-06648671 defined in healthy adult subjects (part 1) Receives: Drug: PF-06648671; Drug: Placebo |
| Multiple Doses PF-06648671 (cohort 8) | Experimental | Healthy subjects receive 14-day repeated dose once a day at 360 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 15, 24 hours post last dose Receives: Drug: PF-06648671; Drug: Placebo |
| Midazolam DDI (optional cohort 9) | Experimental | Healthy Subjects receive single dose of 2 mg midazolam in period 1 followed by 14 days PF-06648671 once a day and coadministration of PF-06648671 and midazolam 2 mg in period 2 (Optional cohort) Receives: Drug: PF-06648671; Drug: Midazolam |
| Multiple Doses PF-06648671 (cohort 6) | Experimental | Healthy subject receive 14-day repeated dose once a day at 200 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 25, 24 hours after last dosing on day 14 Receives: Drug: PF-06648671; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed PF-06648671 Plasma Concentration (Cmax)
Cmax on day 1, 7 and day 14 in part 1, Cmax on day 1 and 14 in part 2
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
PF-06648671 Plasma Area Under the Curve from Time Zero to 24 hour after dosing (AUC24)
AUC24 on day 1, 7 and 14 in part 1, day 1 and 14 in part 2
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Time to Reach Maximum Observed Plasma concentration (Tmax)
Tmax on day 1, 7 and 14 in part 1, day 1 and 14 in part 2
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Plasma Decay half life
t1/2 post last dose on Day 14
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Oral clearance (CL/F)
CL/F on day 14
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Volume of distribution (Vz/F)
Vz/F on day 14
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Observed PF-06648671 CSF concentration
PF-06648671 CSF concentration on day 1 and day 14 (cohort 3) or day 15 (cohorts 5, 6 and 8) prior to dosing in part 1
Measured: 0 hr on day 1 and 0 hr on day 14 or 15
Accumulation factor of AUC24
accumulation of PF-06648671 plasma AUC24 on day 7 and day 14 relative to day 1 in part 1, AUC on day 14 relative to day 1 in part 2
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Accumulation factor of Cmax
PF-06648671 plasma Cmax on day 7 and 14 relative to day 1 in part 1, day 14 to day 1 in part 2
Measured: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
% parent drug in urine (Ae%)
percentage of parent drug recovered in urine over 24 hours on day 14 in part 1 and part 2
Measured: 0-24 hr on day 14
Renal clearance (CLr)
Renal clearance of PF-06648671 on day 14
Measured: 0-24 hours on day 14
CSF Abeta 40 and 42 concentration change from baseline
CSF Abeta 40 and 42 concentration on day 14 (cohort 3) or on day 15 (cohorts 5, 6 and 8) prior to dosing compared to day 1 baseline
Measured: 0 hr on day 1 and 0 hr on day 14 or 15
Plasma AUC of midazolam alone vs co-administration with PF-06648671 in optional part 3
the AUC ratio of midazolam between day 14 in period 2 vs day 1 in period 1 in optional part 3
Measured: 0-24hr on day 1 and 0-48hr on day 14
Plasma Cmax of midazolam alone vs co-administration with PF-06648671 in optional part 3
the Cmax ratio of midazolam between day 14 in period 2 vs day 1 in period 1 in optional part 3
Measured: 0-24hr on day 1 and 0-48hr on day 14
Secondary outcomes (2)
CSF Abeta 37, 38 and total concentration change from baseline
if possible, CSF abeta 37, 38 and total concentration on day 14 prior to dosing compared to day 1 prior to dosing in cohort 3 to 5 in part 1 only
Measured: 0 hr on day 1 and 0 hr on day 14
Plasma Abeta change from baseline
Plasma abeta 40 and 42 and total abeta concentration change from baseline at multiple timepoints
Measured: 0-24hr on day 1 and 0-72hr on day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy Adult Subjects and Healthy Elderly SubjectsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02440100
- Sponsor's protocol ID
- B7991002
- Other IDs
- 2015-000926-13, 2015
- Status last verified
- Nov 2016
- First submitted
- 7 May 2015
- Last updated
- 10 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Ahn JE, Carrieri C, Dela Cruz F, Fullerton T, Hajos-Korcsok E, He P, Kantaridis C, Leurent C, Liu R, Mancuso J, Mendes da Costa L, Qiu R. Pharmacokinetic and Pharmacodynamic Effects of a gamma-Secretase Modulator, PF-06648671, on CSF Amyloid-beta Peptides in Randomized Phase I Studies. Clin Pharmacol Ther. 2020 Jan;107(1):211-220. doi: 10.1002/cpt.1570. Epub 2019 Sep 11.
PubMed 31314925
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-and-subject Blind, Phase 1 Study To Characterize The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Repeat Doses Of Pf-06648671 In Healthy Adult Subjects And Healthy Elderly Subjects
- ClinicalTrials.gov ID
- NCT02440100
- Acronym / sponsor ID
- B7991002
- Keywords
- Phase 1, Multiple doses of PF-06648671, safety, tolerability, PK, plasma and CSF abeta, drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 12 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an investigator-and-subject blind, phase 1 study to characterize the safety, tolerability, pharmacokinetics and central and peripheral pharmacodynamics of 14-day repeated ascending doses of PF-06648671 once a day in healthy adults (part 1) and repeated doses at the maximum tolerated dose (MTD) defined in part 1 in healthy elderly subjects (part 2). The study also include an optional cohort (part 3) to evaluate the drug interaction between PF-06648671 at MTD and CYP3A probe, midazolam
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Multiple Doses PF-06648671 (Cohort1) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subjects receive 14-day repeated dose once a day at 4 mg of PF-06648671 or matching placebo |
| Multiple Doses PF-06648671 (cohort 2) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subject receive 14-day repeated dose once a day at 12 mg of PF-06648671 or matching placebo |
| Multiple doses PF-06648671 (cohort 3) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subject receive 14-day repeated dose once a day at 40 mg of PF-06648671 or matching placebo and CSF LP is collected at baseline and steady state predose on day 1 and 14 |
| Multiple Doses PF-06648671 (cohort 4) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subject receive 14-day repeated dose once a day at 40 mg of PF-06648671 or matching placebo |
| Multiple Doses PF-06648671 (cohort 5) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subject receive 14-day repeated dose once a day at 100 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 15, 24 hours after last dosing on day 14 |
| Multiple Doses in Healthy Elderly (cohort 7) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy Elderly subjects receive 14-day repeated dose once a day at MTD PF-06648671 defined in healthy adult subjects (part 1) |
| Multiple Doses PF-06648671 (cohort 8) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subjects receive 14-day repeated dose once a day at 360 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 15, 24 hours post last dose |
| Midazolam DDI (optional cohort 9) | Experimental | Drug: PF-06648671, Drug: MidazolamHealthy Subjects receive single dose of 2 mg midazolam in period 1 followed by 14 days PF-06648671 once a day and coadministration of PF-06648671 and midazolam 2 mg in period 2 (Optional cohort) |
| Multiple Doses PF-06648671 (cohort 6) | Experimental | Drug: PF-06648671, Drug: PlaceboHealthy subject receive 14-day repeated dose once a day at 200 mg of PF-06648671 or matching placebo, CSF LP is collected at baseline 72 hours prior to day 1 dosing and at steady-state on Day 25, 24 hours after last dosing on day 14 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:
- For Part 1 and Part 3 specific: Healthy female subjects of non childbearing potential and male subjects who, at the time of screening, are 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).
- For Part 2 specific: Female subjects of non childbearing potential and male subjects who, at the time of screening, are between the age of 65 and 85 years, inclusive. Subjects must be in good health as determined by the Investigator based on a detailed medical history, full physical examination (including blood pressure and pulse rate measurement), 12 lead ECG and clinical laboratory tests. Subjects with mild, chronic, stable disease eg, controlled hypertension, non insulin dependent diabetes, osteoarthritis may be enrolled if deemed medically prudent by the investigator. Subjects taking daily prescription or non prescription medications for management of acceptable chronic medical conditions must be on a stable dose of these, as defined by non change in dose for the 3 months prior to the first dose of study medication and no planned changes during the conduct of the study.
- Female subjects of non childbearing potential must meet at least one of the following criteria:
- Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
Key exclusion criteria (28 listed)
- For Part 1 and Part 3 specific: 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) at the discretion of the investigator.
- For Part 2 specific: Recent (eg, last 6 months) evidence or history of unstable disease or moderate to severe conditions which would, in the Investigator's opinion, interfere with the study evaluations or impact on the safety of participating subjects including but not limited to anemia, liver disease, stroke.
- Any condition possibly affecting drug absorption (eg, gastrectomy).
- A positive urine drug screen.
- History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-06648671experimental Pfizer compound which will be dosed as oral suspension, once a day for 14 days | Drug | Midazolam DDI (optional cohort 9), Multiple Doses PF-06648671 (Cohort1), Multiple Doses PF-06648671 (cohort 2), Multiple Doses PF-06648671 (cohort 4), Multiple Doses PF-06648671 (cohort 5), Multiple Doses PF-06648671 (cohort 6), Multiple Doses PF-06648671 (cohort 8), Multiple Doses in Healthy Elderly (cohort 7), Multiple doses PF-06648671 (cohort 3) |
| Midazolamcommercial available oral solution of 2 mg midazolam as CYP3A probe substrate for drug interaction evaluation. Midazolam will be given as single dose with and without co-administration of PF-06648671 | Drug | Midazolam DDI (optional cohort 9) |
| PlaceboMatching placebo which will be given as oral suspension, once a day for 14 days | Drug | Multiple Doses PF-06648671 (Cohort1), Multiple Doses PF-06648671 (cohort 2), Multiple Doses PF-06648671 (cohort 4), Multiple Doses PF-06648671 (cohort 5), Multiple Doses PF-06648671 (cohort 6), Multiple Doses PF-06648671 (cohort 8), Multiple Doses in Healthy Elderly (cohort 7), Multiple doses PF-06648671 (cohort 3) |
Primary outcome
Maximum Observed PF-06648671 Plasma Concentration (Cmax)
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Cmax on day 1, 7 and day 14 in part 1, Cmax on day 1 and 14 in part 2
PF-06648671 Plasma Area Under the Curve from Time Zero to 24 hour after dosing (AUC24)
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
AUC24 on day 1, 7 and 14 in part 1, day 1 and 14 in part 2
Time to Reach Maximum Observed Plasma concentration (Tmax)
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Tmax on day 1, 7 and 14 in part 1, day 1 and 14 in part 2
Plasma Decay half life
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
t1/2 post last dose on Day 14
Oral clearance (CL/F)
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
CL/F on day 14
Volume of distribution (Vz/F)
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
Vz/F on day 14
Observed PF-06648671 CSF concentration
Time frame: 0 hr on day 1 and 0 hr on day 14 or 15
PF-06648671 CSF concentration on day 1 and day 14 (cohort 3) or day 15 (cohorts 5, 6 and 8) prior to dosing in part 1
Accumulation factor of AUC24
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
accumulation of PF-06648671 plasma AUC24 on day 7 and day 14 relative to day 1 in part 1, AUC on day 14 relative to day 1 in part 2
Accumulation factor of Cmax
Time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14
PF-06648671 plasma Cmax on day 7 and 14 relative to day 1 in part 1, day 14 to day 1 in part 2
% parent drug in urine (Ae%)
Time frame: 0-24 hr on day 14
percentage of parent drug recovered in urine over 24 hours on day 14 in part 1 and part 2
Renal clearance (CLr)
Time frame: 0-24 hours on day 14
Renal clearance of PF-06648671 on day 14
CSF Abeta 40 and 42 concentration change from baseline
Time frame: 0 hr on day 1 and 0 hr on day 14 or 15
CSF Abeta 40 and 42 concentration on day 14 (cohort 3) or on day 15 (cohorts 5, 6 and 8) prior to dosing compared to day 1 baseline
Plasma AUC of midazolam alone vs co-administration with PF-06648671 in optional part 3
Time frame: 0-24hr on day 1 and 0-48hr on day 14
the AUC ratio of midazolam between day 14 in period 2 vs day 1 in period 1 in optional part 3
Plasma Cmax of midazolam alone vs co-administration with PF-06648671 in optional part 3
Time frame: 0-24hr on day 1 and 0-48hr on day 14
the Cmax ratio of midazolam between day 14 in period 2 vs day 1 in period 1 in optional part 3
2 secondary outcomes
CSF Abeta 37, 38 and total concentration change from baseline
Time frame: 0 hr on day 1 and 0 hr on day 14
Plasma Abeta change from baseline
Time frame: 0-24hr on day 1 and 0-72hr on day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2016.
- Derived from this study: PubMed 31314925Ahn JE, Carrieri C, Dela Cruz F, Fullerton T, Hajos-Korcsok E, He P, Kantaridis C, Leurent C, Liu R, Mancuso J, Mendes da Costa L, Qiu R. Pharmacokinetic and Pharmacodynamic Effects of a gamma-Secretase Modulator, PF-06648671, on CSF Amyloid-beta Peptides in Randomized Phase I Studies. Clin Pharmacol Ther. 2020 Jan;107(1):211-220. doi: 10.1002/cpt.1570. Epub 2019 Sep 11.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-06648671 and Midazolam in people with Healthy Adult Subjects and Healthy Elderly Subjects, run by Pfizer at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Observed PF-06648671 Plasma Concentration (Cmax) (time frame: 0-24 hours on day 1 and 7 and 0-72 hours on day 14). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02440100, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2016.