Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

NCT02873650 | Terminated Phase 1 FDA Drug

• 1 other identifier: CDRB436A2107
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with moderate and severe hepatic impairment.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Healthy volunteers; Clinical pharmacology study; DRB436; dabrafenib; normal hepatic function; impaired hepatic function

Outcome Measures

Primary Outcomes (8)

• Maximum plasma concentration (Cmax)

  Predose through 96 hours postdose

• Area under the curve (AUClast)

  Predose through 96 hours postdose

• Area under the curve (AUFinf)

  Predose through 96 hours postdose

• Systemic drug clearance (CL/F)

  Predose through 96 hours postdose

• Time to reach maximum concentration (Tmax)

  Predose through 96 hours postdose

• Terminal elimination rate (Lambda_z)

  Predose through 96 hours postdose

• Elimination half-life (T1/2)

  Predose through 96 hours postdose

• Volume of distribution (Vz/F)

  Predose through 96 hours postdose

Secondary Outcomes (7)

• Number of subjects with adverse events

  Time of study drug administration through 30 days postdose

• Number of subjects with abnormal lab values related to study drug

  Time of study drug administration through 30 days postdose

• Number of subjects with abnormal blood pressure related to study drug

  Time of study drug administration through 30 days postdose

• Number of subjects with abnormal pulse rate related to study drug

  Time of study drug administration through 30 days postdose

• Number of subjects with abnormal respiratory rate related to study drug

  Time of study drug administration through 30 days postdose

Study Arms (3)

Group 1 - Control group

EXPERIMENTAL

Drug: dabrafenib

Group 2-Moderate hepatic impairment

EXPERIMENTAL

Drug: dabrafenib

Group 3-Severe hepatic impairment

EXPERIMENTAL

Drug: dabrafenib

Interventions

dabrafenib DRUG

Single dose of 100 mg dabrafenib on Day 1

Also known as: DRB436

Group 1 - Control group; Group 2-Moderate hepatic impairment; Group 3-Severe hepatic impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and/or female subjects 18-75 years of age
• Females must be of non-childbearing potential . All non-postmenopausal females must have a confirmed negative serum pregnancy
• Subjects in good health condition as determined by no clinically significant findings from medical history and physical examination.
• Body mass index (BMI) between ≥18.0 and ≤38.0 kg/m2, with body weight ≥ 50 kg and no more than 140 kg
• Laboratory values must be within normal limits (correction allowed) or considered clinically insignificant
• Do not participate in any other clinical trials with a BRAF or other RAF inhibitors
• Absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms and clinical laboratory determinations.
• Must match to at least one hepatic impairment subject by age, gender and bodyweight
• Confirmed hepatic disease
• Stable Child-Pugh status within 28 days prior to dosing.

You may not qualify if:

• Participation in any clinical investigation within 4 weeks prior to dosing
• Significant acute illness within the two weeks prior to dosing
• History of immunodeficiency diseases, including a positive HIV
• History of malignancy of any organ system, treated or untreated, within 5 years
• Any prior history of keratoacanthoma and/or cutaneous squamous cell carcinoma
• A known diagnosis of any of the RASopathies, such as NF-1, Noonan syndrome, or related conditions.
• History of drug or alcohol abuse within the 6 months prior to dosing
• Smoking: urine cotinine levels below 500 ng/mL on Day -1.
• Use of drugs known to affect CYP3A4 and/or CYP2C8 including both (strong or moderate) inhibitors and inducers, within 7 days prior to dosing
• Administration of medications that prolong the QT interval within 4 weeks prior to dosing and until EOT.
• History or current diagnosis of cardiac disease indicating significant risk of safety
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.
• Clinical evidence of liver disease or liver injury
• History or presence of renal impairment as indicated by abnormal creatinine or BUN values
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

American Institute of Research

Los Angeles, California, 900017, United States

Location

Omega Research Consultants LLC

DeBary, Florida, 32713, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Wake Research Associates Oncology

Raleigh, North Carolina, 27612, United States

Location

Related Links

• Related Info

MeSH Terms

Interventions

dabrafenib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open-label, parallel group

Study Record Dates

• First Submitted: August 16, 2016
• First Posted: August 19, 2016
• Study Start: December 20, 2016
• Primary Completion: October 12, 2018
• Study Completion: April 8, 2019
• Last Updated: December 8, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)