Hepatic ImpairmentPhase 1NCT03309202
Study of PF-05221304 in Subjects With Varying Degrees of Hepatic Impairment
A Phase 1 study testing PF-05221304 in people with Hepatic Impairment, run by Pfizer at 6 sites in 4 countries.
Trial summary
Hepatic impairment PK study Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- PF-05221304
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 19 Dec 2017to 18 Jul 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- All subjects -
- Adults <18 years of age and >70 years of age
- BMI < 17.5 and > 35.4 kg/m2
- HIV positive
- Conditions that affect drug absorption
- Positive breath alcohol test
Show all 16Show fewer
- Healthy/ those without hepatic impairment -
- Known or suspected hepatic impairment
- Evidence of Hepatitis B or C
- On any chronic medications
- Those with varying degrees of hepatic impairment -
- Not meeting Classification A, B, or C of hepatic impairment based on Child-Pugh Classification
- Evidence of Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy
- Recent GI bleed
- Moderate or severe renal impairment
- Hepatic encephalopathy Grade 3 or higher
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Czechia2 sites
Pharmaceutical Research Associates CZ, s.r.o.
Prague, 170 00
Nemocnice Na Bulovce
Prague, 180 81
Slovakia2 sites
Summit Clinical Research s.r.o.
Bratislava, 83101
Univerzitná Nemocnica Bratislava
Bratislava, 83305
United States1 site
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-05221304 IN ADULT SUBJECTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITHOUT HEPATIC IMPAIRMENT
Hepatic impairment PK study
Read the detailed description
This is a non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (total and unbound) of PF-05221304 after a single oral dose administered in the fed state.
- Conditions
- Hepatic Impairment
- Being tested
- PF-05221304
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-05221304Drug
Also called experimental drug
25 mg dose
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1_Without impairment | Experimental | Single, 25 mg dose of PF-05221304 Receives: Drug: PF-05221304 |
| Cohort 2_Mild impairment | Experimental | Single, 25 mg dose of PF-05221304 Receives: Drug: PF-05221304 |
| Cohort 3_Moderate impairment | Experimental | Single, 25 mg dose of PF-05221304 Receives: Drug: PF-05221304 |
| Cohort 4_Severe impairment | Experimental | Single, 25 mg dose of PF-05221304 Receives: Drug: PF-05221304 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of PF-05221304
Cmax was observed directly from data.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304
AUCinf was calculated by AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Fraction Unbound (fu) of PF-05221304
fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Measured: 4 hours postdose
Unbound Cmax (Cmax,u) of PF-05221304
Cmax,u was calculated by fu*Cmax.
Measured: 4 hours postdose
Unbound AUCinf (AUCinf,u) of PF-05221304
AUCinf,u was calculated by fu*AUCinf.
Measured: 4 hours postdose
Secondary outcomes (14)
Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304
Tmax was observed directly from data as time of first occurrence.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304
AUClast was calculated by linear/Log trapezoidal method.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Unbound AUClast ( AUClast,u) of PF-05221304
AUClast,u was calculated by fu*AUClast.
Measured: 4 hours postdose
Apparent Clearance After Oral Dose (CL/F) of PF-05221304
CL/F was calculated by Dose/AUCinf.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Unbound CL/F (CLu/F) of PF-05221304
CLu/F was calculated by fu*CL/F.
Measured: 4 hours postdose
Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304
Vz/F was calculated by Dose/(AUCinf*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Unbound Vz/F (Vz,u/F) of PF-05221304
Vz,u/F was calculated by fu*Vz/F.
Measured: 4 hours postdose
Terminal Half-Life ( t½) of PF-05221304
t1/2 was calculated by loge(2)/kel.
Measured: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.
Measured: Approximately 30 days
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, reticulocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration (MCHC), erythrocyte mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time and prothrombin time.
Measured: 7 days
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Clinical chemistry evaluation included: bilirubin, direct/indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase , alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, phosphate, bicarbonate, creatine kinase, and fasting glucose.
Measured: 7 days
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Urinalysis evaluation included: scalar urine glucose, scalar ketones, scalar urine protein, scalar urine hemoglobin, scalar urobilinogen, scalar urine bilirubin, scalar nitrite, scalar leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and scalar bacteria.
Measured: 7 days
Number of Participants With Clinical Significant Findings in Vital Signs
Vital signs evaluation included: sitting systolic and diastolic blood pressure (BP), and sitting pulse rate. Clinically significant findings in vital signs were determined by the investigator.
Measured: 7 days
Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data
ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and heart rate. Clinically significant findings in ECG data were determined by the investigator.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start19 Dec 2017
- Primary completion26 Jun 2018
- Study completion18 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic ImpairmentStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 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
- NCT03309202
- Sponsor's protocol ID
- C1171006
- Other IDs
- 2017-003034-86, 2017
- Status last verified
- Jun 2019
- First submitted
- 10 Oct 2017
- Last updated
- 8 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-05221304 IN ADULT SUBJECTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITHOUT HEPATIC IMPAIRMENT
- ClinicalTrials.gov ID
- NCT03309202
- Acronym / sponsor ID
- C1171006
- Conditions
- Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 19 Dec 2017 (actual)
- Primary completion
- 26 Jun 2018 (actual)
- Study completion
- 18 Jul 2018 (actual)
- First posted
- 13 Oct 2017 (actual)
- Results
- Posted 8 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatic impairment PK study
Detailed description
This is a non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (total and unbound) of PF-05221304 after a single oral dose administered in the fed state.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1_Without impairment | Experimental | Drug: PF-05221304Single, 25 mg dose of PF-05221304 |
| Cohort 2_Mild impairment | Experimental | Drug: PF-05221304Single, 25 mg dose of PF-05221304 |
| Cohort 3_Moderate impairment | Experimental | Drug: PF-05221304Single, 25 mg dose of PF-05221304 |
| Cohort 4_Severe impairment | Experimental | Drug: PF-05221304Single, 25 mg dose of PF-05221304 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- All subjects -
- Adults <18 years of age and >70 years of age
- BMI < 17.5 and > 35.4 kg/m2
- HIV positive
- Conditions that affect drug absorption
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-05221304Also: experimental drug25 mg dose | Drug | Cohort 1_Without impairment, Cohort 2_Mild impairment, Cohort 3_Moderate impairment, Cohort 4_Severe impairment |
Primary outcome
Maximum Plasma Concentration (Cmax) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Cmax was observed directly from data.
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
AUCinf was calculated by AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Fraction Unbound (fu) of PF-05221304
Time frame: 4 hours postdose
fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Unbound Cmax (Cmax,u) of PF-05221304
Time frame: 4 hours postdose
Cmax,u was calculated by fu*Cmax.
Unbound AUCinf (AUCinf,u) of PF-05221304
Time frame: 4 hours postdose
AUCinf,u was calculated by fu*AUCinf.
14 secondary outcomes
Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Unbound AUClast ( AUClast,u) of PF-05221304
Time frame: 4 hours postdose
Apparent Clearance After Oral Dose (CL/F) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Unbound CL/F (CLu/F) of PF-05221304
Time frame: 4 hours postdose
Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Unbound Vz/F (Vz,u/F) of PF-05221304
Time frame: 4 hours postdose
Terminal Half-Life ( t½) of PF-05221304
Time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Approximately 30 days
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Time frame: 7 days
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Time frame: 7 days
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Time frame: 7 days
Number of Participants With Clinical Significant Findings in Vital Signs
Time frame: 7 days
Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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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
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-05221304 in people with Hepatic Impairment, run by Pfizer at 6 sites in 4 countries.
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 0 inclusion and 16 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 8 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Czechia, Slovakia, United States, 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?
Yes. Results are posted in the registry (first posted 8 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Plasma Concentration (Cmax) of PF-05221304 (time frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose). The study lists 5 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 8 Aug 2019.