MigrainePhase 1NCT01981486
A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults
A Phase 1 study testing PF-05180999 Tablets in people with Migraine, run by Pfizer.
Trial summary
PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine
- What is being tested?
- PF-05180999 Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2014to Jan 2015
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years
- Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)
Who cannot join
- Subjects with Gilbert's disease or screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal.
- Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C.
- Subjects with very light skin or very dark skin (at the discretion of the investigator).
About this study
Official title: A Phase I, Placebo Controlled, Randomized, Subject-And Investigator-Blind, Sponsor-Open, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-05180999 In Healthy Adult Volunteers
PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid.
- Conditions
- Migraine
- Being tested
- Placebo Tablets, PF-05180999 Tablets
- Keywords
- PF-05180999, safety, tolerability, pharmacokinetics, migraine, PDE2, cAMP, cGMP, cantharidin, blister, CYP3A induction
- Medical subject headings
- Migraine Disorders, Blister
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo TabletsDrug
BID modified-release tablets
PF-05180999 TabletsDrug
BID modified-release tablets (20 to 240 mg BID)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo tablets Receives: Drug: Placebo Tablets |
| PF-05180999 | Experimental | Modified-release tablets of PF-05180999 Receives: Drug: PF-05180999 Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax)
Single dose Cmax
Measured: 0-12 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Single dose Tmax
Measured: 0-12 hours post-dose on Day 1
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
Single dose AUCtau
Measured: 0-12 hours post-dose on Day 1
Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
Steady-state Cmax
Measured: 0-12 hours post-dose on Day 14
Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
Steady-state Tmax
Measured: 0-12 hours post-dose on Day 14
Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
Steady-state Cmin
Measured: 0-12 hours post-dose on Day 14
Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
Steady-state AUCtau
Measured: 0-12 hours post-dose on Day 14
Apparent Oral Clearance (CL/F)
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.
Measured: 0-48 hours post-final dose on Day 14
Apparent Volume of Distribution (Vz/F)
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.
Measured: 0-48 hours post-final dose on Day 14
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 0-48 hours post-final dose on Day 14
Accumulation Ratio (Racc)
Ratio of Day 14 AUCtau to Day 1 AUCtau
Measured: 0-12 hours post-dose on Days 1 and 14
Amount Excreted in Urine (Ae)
Amount of drug excreted in urine
Measured: 0-12 hours post-dose on Day 14
Percent of Dose Excreted in Urine (Ae%)
Percent of total dose excreted in urine
Measured: 0-12 hours post-dose on Day 14
Renal Clearance (CLr)
Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.
Measured: 0-48 hours post-dose on Day 14
Secondary outcomes (7)
Identification of metabolites of PF-05180999 in urine and plasma
Metabolite identification
Measured: 0-12 hours post-dose on Day 14
Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood
Leukocyte levels in blister fluid and blood
Measured: Day 13 and Day 14
Change from Baseline in Cytokine Levels in Blister Fluid
Cytokine levels in blister fluid
Measured: Day 13 and Day 14
Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP
Time-averaged area under the effect curve
Measured: 0-12 hours post-dose on Day 1 and Day 14
AUEC/t Ratio
Ratio of Day 14 AUEC/t to Day 1 AUEC/t
Measured: 0-12 hours post-dose on Day 1 and Day 14
Urinary 6beta-hydroxycortisol/cortisol ratio
Urinary marker of CYP3A induction
Measured: Day 14
Plasma 4beta-hydroxycholesterol/cholesterol ratio
Plasma marker of CYP3A induction
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2013 (estimated)
- Study startJun 2014
- Primary completionJan 2015 (estimated)
- Study completionJan 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MigraineStudies 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
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
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
- NCT01981486
- Sponsor's protocol ID
- B3441008
- Status last verified
- May 2014
- First submitted
- 5 Nov 2013
- Last updated
- 23 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Placebo Controlled, Randomized, Subject-And Investigator-Blind, Sponsor-Open, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-05180999 In Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT01981486
- Acronym / sponsor ID
- B3441008
- Conditions
- Migraine
- Keywords
- PF-05180999, safety, tolerability, pharmacokinetics, migraine, PDE2, cAMP, cGMP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jun 2014
- Primary completion
- Jan 2015 (estimated)
- Study completion
- Jan 2015 (estimated)
- First posted
- 11 Nov 2013 (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.
PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo TabletsPlacebo tablets |
| PF-05180999 | Experimental | Drug: PF-05180999 TabletsModified-release tablets of PF-05180999 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years
- Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)
Key exclusion criteria (3 listed)
- Subjects with Gilbert's disease or screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal.
- Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C.
- Subjects with very light skin or very dark skin (at the discretion of the investigator).
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 |
|---|---|---|
| Placebo TabletsBID modified-release tablets | Drug | Placebo |
| PF-05180999 TabletsBID modified-release tablets (20 to 240 mg BID) | Drug | PF-05180999 |
Primary outcome
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0-12 hours post-dose on Day 1
Single dose Cmax
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0-12 hours post-dose on Day 1
Single dose Tmax
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
Time frame: 0-12 hours post-dose on Day 1
Single dose AUCtau
Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
Time frame: 0-12 hours post-dose on Day 14
Steady-state Cmax
Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
Time frame: 0-12 hours post-dose on Day 14
Steady-state Tmax
Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
Time frame: 0-12 hours post-dose on Day 14
Steady-state Cmin
Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
Time frame: 0-12 hours post-dose on Day 14
Steady-state AUCtau
Apparent Oral Clearance (CL/F)
Time frame: 0-48 hours post-final dose on Day 14
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Volume of Distribution (Vz/F)
Time frame: 0-48 hours post-final dose on Day 14
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.
Plasma Decay Half-Life (t1/2)
Time frame: 0-48 hours post-final dose on Day 14
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Accumulation Ratio (Racc)
Time frame: 0-12 hours post-dose on Days 1 and 14
Ratio of Day 14 AUCtau to Day 1 AUCtau
Amount Excreted in Urine (Ae)
Time frame: 0-12 hours post-dose on Day 14
Amount of drug excreted in urine
Percent of Dose Excreted in Urine (Ae%)
Time frame: 0-12 hours post-dose on Day 14
Percent of total dose excreted in urine
Renal Clearance (CLr)
Time frame: 0-48 hours post-dose on Day 14
Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.
7 secondary outcomes
Identification of metabolites of PF-05180999 in urine and plasma
Time frame: 0-12 hours post-dose on Day 14
Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood
Time frame: Day 13 and Day 14
Change from Baseline in Cytokine Levels in Blister Fluid
Time frame: Day 13 and Day 14
Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP
Time frame: 0-12 hours post-dose on Day 1 and Day 14
AUEC/t Ratio
Time frame: 0-12 hours post-dose on Day 1 and Day 14
Urinary 6beta-hydroxycortisol/cortisol ratio
Time frame: Day 14
Plasma 4beta-hydroxycholesterol/cholesterol ratio
Time frame: Day 14
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2014.
- 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
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-05180999 Tablets in people with Migraine, run by Pfizer.
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 2 inclusion and 3 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: withdrawn, as of the sponsor's last update on 23 May 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 was withdrawn before enrolling participants, so there are no results.
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 Plasma Concentration (Cmax) (time frame: 0-12 hours post-dose on Day 1). 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?
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 23 May 2014.