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Hepatic ImpairmentPhase 1NCT06084104

DZD9008 PK Study in Hepatic Impairment Subjects

A Phase 1 study testing DZD9008 in people with Hepatic Impairment, run by Dizal Pharmaceuticals at 2 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 study will investigate the pharmacokinetics, safety, and tolerability of DZD9008 in subjects with hepatic impairment compared to subjects with normal hepatic function Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Hepatic Impairment
What is being tested?
DZD9008
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesUnited States
Study dates
17 Oct 2023to 23 Oct 2024
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 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • The subject is male or female 18 to 75 years of age, inclusive, at screening.
  • The subject has a BMI of 18.0 to 40.0 kg/m2, inclusive, at screening and check-in.
  • The subject has a minimum body weight of 50.0 kg, at screening and check-in.
  • The subject has a resting pulse rate of ≥ 40 and < 100 beats per minute with no clinically significant deviation as judged by the investigator.
  • The subject agrees to comply with all protocol requirements.
  • The subject is able to provide written informed consent.
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  • Additional Inclusion Criteria for Healthy Subjects Only (Cohort 2) Only (7-11):
  • The subject has normal hepatic function. No known or suspected hepatic impairment based on liver function tests (e.g., ALT, AST, ALP, and bilirubin), albumin, and prothrombin time is defined as the following with a single repeat permitted to assess eligibility if needed, at screening and check-in:
  • ALT and AST ≤ ULN
  • Total bilirubin ≤ ULN (subjects with a history of Gilbert syndrome are eligible if they only have elevated total bilirubin)
  • ALP ≤ ULN
  • Albumin ≥ 3.6 g/dL
  • Prothrombin time ≤ ULN
  • The subject has a resting blood pressure of 90 to 145 mmHg (systolic) and 40 to 95 mmHg (diastolic), at screening and check-in.
  • The subject has a QTcF of ≤ 450 msec, at screening and check-in.
  • The subject is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12 lead ECG results, and physical examination findings.
  • Each subject with normal hepatic function (Cohort 2) must individually match a subject with impaired hepatic function (Cohort 1) by age (± 10 years), body weight (± 10 kg), and sex (similar distribution of males and females).
  • Additional Inclusion Criteria for Subjects with Hepatic Impairment (Cohort 1) Only (12-18):
  • The subject satisfies the Class B of the Child-Pugh classification (no albumin use within 14 days). Six out of 10 subjects also meet NCI ODWG Group C criteria.
  • The subject has a diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process), with features of cirrhosis due to any etiology, except for DILI, which is confirmed by at least one of the following criteria:
  • histologically by prior liver biopsy showing cirrhosis
  • clinically by physical examination, laboratory data, liver imaging, or endoscopic findings
  • The subject has following clinical laboratory values, at screening and check-in:
  • ALT and AST ≤ 5 × ULN
  • Total bilirubin ≤ 3 × ULN
  • ANC ≥ 1.5 × 109/L
  • Platelet count ≥ 30 × 109/L
  • Hemoglobin ≥ 90 g/L
  • The subject has chronic (more than 6 months) and stable hepatic impairment (ie, no acute episodes of illness within 30 days before screening due to deterioration of hepatic function) as assessed by the NCI-ODWG criteria (Group C) or a Child-Pugh classification score of moderate (7 to 9 points).
  • The subject has a resting blood pressure of 90 to 155 mmHg (systolic) and 50 to 100 mmHg (diastolic), at screening and check-in.
  • The subject has a QTcF of ≤ 470 msec, at screening and check-in.
  • The subject is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12 lead ECG results, and physical examination findings, except for findings that, as judged by the investigator, are consistent with the subject's hepatic impairment or other stable concomitant medical conditions.

Who cannot join

  • The subject has a history or clinical manifestations of a significant neurological, renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, or psychiatric disease that would preclude study participation, as judged by the investigator.
  • The subject has any surgical or medical condition that may alter the absorption, distribution, metabolism, or excretion of drugs (e.g., gastrectomy).
  • The subject has a history of cancer (malignancy) with the following exceptions:
  • adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix, or
  • other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study
  • The subject has a history of being immunocompromised or has a positive test result for HIV types 1 or 2 antibodies at screening.
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  • The subject has an acute or chronic infection requiring treatment with oral antibiotics (except, rifaximin for the treatment of hepatic encephalopathy), antivirals, antiparasitic, antiprotozoals, or antifungals within 4 weeks prior to Day 1 or superficial skin infection within 1 week prior to Day 1.
  • The subject has a history of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of long QT syndrome), has clinically significant hypokalemia or hypomagnesemia, and is taking concomitant medications that prolong the QT/QTc interval.
  • The subject has uncontrolled hypertension despite optimal medical management.
  • The subject had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study drug administration.
  • The subject tests positive for breath alcohol test at screening and on check-in (Day 1).
  • The subject is unable or unwilling to restrict smoking to 5 cigarettes or less per day.
  • The subject is involved in strenuous activity or contact sports within 24 hours of the first dose of study drug or during the study.
  • The subject has donated blood (excluding plasma donation) of ≥ 500 mL within 60 days before the first dose of study drug.
  • The subject has poor peripheral venous access.
  • The subject should not be any of the following:
  • investigator staff member or their family members
  • site staff member otherwise supervised by the investigator, or employees, including their family members, directly involved in the conduct of the study
  • The subject has a history of relevant drug and/or food allergies (ie, allergy to DZD9008 or any excipients, or any significant food allergy).
  • The subject has received DZD9008 or any other investigational drug in another investigational study within 30 days of dosing.
  • The subject is enrolled in another clinical study or has used any investigational drug or device within 4 weeks (or 5 times the half-life of the pervious drug [if known], whichever is longer), prior to dosing with study drug. The window will be derived from the date of the last dose of study drug in the previous study.
  • The subject has used a strong or moderate inhibitor or inducer of CYP3A4 and/or P gp including St. John's Wort, within 14 days and 28 days, respectively, prior to dosing and until the completion of the last PK sample collection unless it is deemed acceptable following consultation with Dizal Pharma's medical monitor and the investigator.
  • The subject has used PPIs within 5 days prior to dosing until 24 hours after dosing. Use of H2-antagonists and antacids within 12 hours prior to dosing until 12 hours after dosing unless it is deemed acceptable following consultation with Dizal Pharma's medical monitor and the investigator.
  • In the opinion of the investigator, the subject is not suitable for entry into the study.
  • Additional Exclusion Criteria for Healthy Subjects Only (Cohort 2):
  • The subject with normal hepatic function has any of the following:
  • evidence or history of bleeding diathesis, or
  • any hemorrhage or moderate bleeding event within 4 weeks of start of study drug administration
  • The subject has a positive result for HBsAg or HCV Ab.
  • The subject has an estimated glomerular filtration rate (CKD-EPI formula or Cockcroft-Gault method) of < 90 mL/min.
  • The subject has used any vaccine or used any prescription (excluding hormonal birth control and hormone replacement therapy) or over the counter medications (except paracetamol [up to 2 g per day]), including herbal or nutritional supplements, within 14 days before the first dose of study drug and throughout the study.
  • The subject has a positive test result for drugs of abuse or alcohol at screening or before the first dose of study drug.
  • Additional Exclusion Criteria for Subjects with Hepatic Impairment Only (Cohort 1):
  • The subject has fluctuating or rapidly deteriorating hepatic function, as indicated by recent history or worsening of clinical (ie, abdominal pain, nausea, vomiting, anorexia, or fever) and/or laboratory signs of hepatic impairment, as judged by the investigator.
  • The subject has evidence of acute viral hepatitis within 30 days before dosing with study drug.
  • The subject has an active hepatitis B or C viral infection.
  • The subject has history or symptoms of hepatic encephalopathy Grade 2 or above within 3 months prior to screening visit.
  • The subject has a history of unstable diabetes mellitus as evidenced by HbA1c ≥ 9% at screening.
  • In the opinion of the investigator, the subject has clinically demonstrable severe ascites and/or pleural effusion.
  • The subject has evidence of hepatopulmonary syndrome, hydrothorax, or hepatorenal syndrome.
  • The subject had an organ transplant or is on a waiting list.
  • The subject had a portosystemic shunt (including transjugular intrahepatic portosystemic shunts).
  • The subject has an estimated glomerular filtration rate (CKD-EPI formula) of < 60 mL/min.
  • The subject has symptoms consistent with spontaneous bacterial peritonitis, known active spontaneous bacterial peritonitis, or a history of spontaneous peritonitis within the last 6 months.
  • The subject is suspected of having hepatocellular carcinoma (ie, if α fetoprotein > 50 ng/mL at screening), subjects will undergo appropriate diagnostic studies (e.g., CT scan or hepatic ultrasound) to exclude the possibility of hepatocellular carcinoma.
  • The subject has received any vaccine or used any prescription (excluding hormonal birth control and hormone replacement therapy) or over the counter medications, including herbal or nutritional supplements, within 14 days before the first dose of study drug and throughout the study, except those essential for the management of hepatic impairment or the treatment of stable concomitant medical conditions, as judged by the investigator. The dose of an approved medication must remain stable from 7 days before study drug dosing and throughout the study.
  • The subject has a positive test result for drugs of abuse (except positive test results associated with prescription medications that have been reviewed and approved by the investigator) or alcohol at screening or prior to study drug dosing.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Orlando Clinical Research Center

    Orlando, Florida, 32809

  • American Research Corporation

    San Antonio, Texas, 78215

Other trials in United States

About this study

Official title: A Phase 1, Single-Dose, Non-Randomized, Open Label Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of DZD9008

This study will investigate the pharmacokinetics, safety, and tolerability of DZD9008 in subjects with hepatic impairment compared to subjects with normal hepatic function

Being tested
DZD9008

What participants receive

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

  • DZD9008Drug

    A single oral dose of 200mg DZD9008

  • DZD9008Drug

    A single oral dose of 200mg DZD9008

Study groups in NCT06084104
Study groupRoleWhat they receive
Hepatic impairmentExperimentalSubjects with hepatic impairment
Receives: Drug: DZD9008
Healthy SubjectExperimentalSubjects with normal hepatic function
Receives: Drug: DZD9008

What is being measured

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

  1. Maximum observed plasma (peak) drug concentration [Cmax]

    Measured: Day 1 to day 14

  2. Area under plasma concentration time curve from zero to infinity (AUCinf)

    Measured: Day 1 to day 14

  3. Area under the plasma concentration-curve from time zero to last quantifiable concentration (AUClast)

    Measured: Day 1 to day 14

Secondary outcomes (15)

  1. Apparent total body clearance (CL/F)

    Measured: Day 1 to day 14

  2. Area under plasma concentration time curve from zero to infinity (AUCinf)

    Measured: Day 1 to day 14

  3. Terminal phase half-life (t1/2),

    Measured: Day 1 to day 14

  4. Time to maximum observed plasma concentration (Tmax)

    Measured: Day 1 to day 14

  5. Fraction unbound (Fu)

    Measured: Day 1 to day 14

  6. Unbound area under plasma concentration time curve from zero to infinity (AUC0-inf, u)

    Measured: Day 1 to day 14

  7. Unbound area under the plasma concentration-curve from time zero to last quantifiable concentration (AUC0-last, u)

    Measured: Day 1 to day 14

  8. Unbound maximum observed plasma (peak) drug concentration (Cmax, u)

    Measured: Day 1 to day 14

  9. Unbound apparent total body clearance (CLu/F)

    Measured: Day 1 to day 14

  10. Unbound apparent volume of distribution (Vz,u/F)

    Measured: Day 1 to day 14

  11. Adverse events

    Measured: Day 1 to day 14

  12. Clinical laboratory test results: hematology, coagulation, serum chemistry, urinalysis

    Measured: Day 1 to day 14

  13. 12-lead ECG results: tracings, rhythm, RR interval, PR interval, QRS width, QT interval, and QTcF

    Measured: Day 1 to day 14

  14. Vital sign measurements: systolic and diastolic blood pressure, pulse rate, respiratory rate and body temperature

    Measured: Day 1 to day 14

  15. Physical examination findings: assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, and musculoskeletal system/extremities

    Measured: Day 1 to day 14

Timeline

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

  1. First posted16 Oct 2023
  2. Study start17 Oct 2023
  3. Primary completion12 Jun 2024
  4. Study completion23 Oct 2024

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
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06084104
Sponsor's protocol ID
DZ2022E0007
Status last verified
Dec 2024
First submitted
6 Sep 2023
Last updated
18 Dec 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DZD9008 in people with Hepatic Impairment, run by Dizal Pharmaceuticals at 2 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 32 inclusion and 47 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 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

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 plasma (peak) drug concentration [Cmax] (time frame: Day 1 to day 14). The study lists 3 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 NCT06084104.

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 18 Dec 2024.

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