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Severe Hepatic ImpairmentPhase 1NCT03865446

Evaluate Severe Hepatic Impairment on Dacomitinib PK

A Phase 1 study testing Dacomitinib in people with Severe Hepatic Impairment, run by Pfizer at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Severe Hepatic Impairment
What is being tested?
Dacomitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
3 sitesUnited States
Study dates
5 Apr 2019to 24 Oct 2019
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 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Participants are eligible to be included in the study only if all of the following criteria apply:
  • Male and/or female participants of non childbearing potential must be 18 to 75 years of age, inclusive, at the time of signing the informed consent document (ICD).
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Weight:
  • Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb).
  • Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Who cannot join

  • Participants are excluded from the study if any of the following criteria apply:
  • Any condition possibly affecting drug absorption (eg, gastrectomy).
  • Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
  • History of or current positive results for human immunodeficiency virus (HIV).
  • Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of IP used in this study (whichever is longer).
  • Hypersensitivity to dacomitinib or its excipients.
Show all 11Show fewer
  • A positive urine drug test. Participants with severe hepatic impairment (Cohort 1) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of dacomitinib.
  • Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
  • History of sensitivity to heparin or heparin induced thrombocytopenia.
  • Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
  • Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy

    Miami, Florida, 33136

  • University of Miami Division of Clinical Pharmacology

    Miami, Florida, 33136

  • Orlando Clinical Research Center

    Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PLASMA PHARMACOKINETICS AND SAFETY OF DACOMITINIB IN PARTICIPANTS WITH SEVERELY IMPAIRED HEPATIC FUNCTION RELATIVE TO PARTICIPANTS WITH NORMAL HEPATIC FUNCTION

This is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib.

Read the detailed description

This is a Phase 1, open label, parallel group study to investigate the effect of severe hepatic impairment on the plasma PK, safety and tolerability after a single oral 30 mg dose of dacomitinib under fasted conditions.

Approximately 18 participants will be enrolled into the study to ensure at least 6 PK evaluable (having data for estimating primary PK parameters for dacomitinib) participants in each cohort.

Being tested
Dacomitinib
Keywords
Pharmacokinetics, Dacomitinib, Hepatic Impairment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DacomitinibDrug

    Also called PF-00299804; VIZIMPRO

    anti-cancer agent

Study groups in NCT03865446
Study groupRoleWhat they receive
Cohort 1 (Dacomitinib)Experimentalsevere hepatic impairment group
Receives: Drug: Dacomitinib
Cohort 2 (Dacomitinib)Experimentalnormal hepatic function
Receives: Drug: Dacomitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Observed Plasma Concentration (Cmax) of Dacomitinib

    Cmax of Dacomitinib was analyzed.

    Measured: Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1

  2. Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib

    AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

    Measured: Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1

Secondary outcomes (5)

  1. Number of Participants With Laboratory Abnormalities

    Laboratory abnormalities included hematology- Erythrocyte mean corpuscular hemoglobin: less than (<) 0.9 *lower limit of normal (LLN), platelets: < 0.5* LLN, leukocytes: < 0.6* LLN, lymphocytes: < 0.8* LLN, eosinophils: greater than (>) 1.2* lower limit of normal (ULN), partial thromboplastin time (PTT): > 1.1* ULN, prothrombin time: > 1.1* ULN, Prothrombin Intl. normalized ratio: > 1.1* ULN, clinical chemistry- bilirubin: > 1.5* ULN, protein: < 0.8* LLN, albumin: < 0.8* LLN, urinalysis- urine protein: greater than or equal to (>=) 1, urine hemoglobin: >= 1, urobilinogen: >= 1, urine erythrocytes: >= 20.

    Measured: Baseline up to Day 7

  2. Number of Participants With Physical Examination Abnormalities

    Height and weight were measured to calculate body mass index abnormality.

    Measured: Baseline up to Day 7

  3. Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern

    Systolic blood pressure, diastolic blood pressure and pulse rate were evaluated for examination of vital signs. Criteria for potential concern in absolute values of vital sign: pulse rate: <40 beats per minute (bpm), >120 beats per minute; supine diastolic blood pressure: <50 millimeter of mercury (mm Hg); supine systolic blood pressure: <90 mm Hg. Criteria for potential concern in change from baseline in vital sign values: supine diastolic blood pressure: greater than or equal to >= 30 mm Hg increase or decrease from baseline; supine diastolic blood pressure: >=20 mm Hg increase or decrease from baseline. Only participants with vital sign parameters meeting criteria of potential clinical concern are reported.

    Measured: Baseline up to Day 7

  4. Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern

    ECG parameters RR interval, PR interval, QRS interval, QT interval, QTC interval, QTCB, QTCF and heart rate were measured. Criteria of potential concern for absolute values: PR interval: >=300 milliseconds; QRS interval >=140 milliseconds; QT interval: >=500 milliseconds; QTCF (Fridericia's correction formula) : >= 450 to < 480 milliseconds, >=480 to <500 milliseconds, >=500 milliseconds. Criteria of potential concern for change from baseline values: PR interval: when baseline is >200 millisecond- change >=25%, when baseline <200 milliseconds- change >=50%; QRS interval: change >= 50%; QTCF: change >=30 to <60, change >=60. In this outcome measure, participants meeting the criteria of potential concern for any of the ECG parameters are reported.

    Measured: Baseline up to Day 7

  5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. 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; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period (Up to Day 35) that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.

    Measured: Baseline up to Day 35

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2019
  2. Study start5 Apr 2019
  3. Primary completion24 Oct 2019
  4. Study completion24 Oct 2019

Resources

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
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03865446
Sponsor's protocol ID
A7471058
Status last verified
Oct 2020
First submitted
7 Feb 2019
Last updated
6 Nov 2020
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.

Publications

  • Piscitelli J, Chen J, LaBadie RR, Salageanu J, Chung CH, Tan W. The Effect of Hepatic Impairment on the Pharmacokinetics of Dacomitinib. Clin Drug Investig. 2022 Mar;42(3):221-235. doi: 10.1007/s40261-022-01125-x. Epub 2022 Feb 23.

    PubMed 35195881

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dacomitinib in people with Severe Hepatic Impairment, run by Pfizer at 3 sites in United States.

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 6 inclusion and 11 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 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 6 Nov 2020). 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 Observed Plasma Concentration (Cmax) of Dacomitinib (time frame: Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1). The study lists 2 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 NCT03865446, 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 6 Nov 2020.

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