A Study to Evaluate Drug-Drug Interactions of Obicetrapib Tablets and Ezetimibe Tablets in Healthy Adult Subjects

A Study to Evaluate Drug-Drug Interactions of Obicetrapib Tablets and Ezetimibe Tablets in Healthy Adult Subjects

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Obicetrapib 10mg; Drug: Ezetimibe 10mg

Detailed Description

A Study to Evaluate the PK of obicetrapib tablets with and without co-administration of daily doses of ezetimibe tablets and the PK of ezetimibe tablets with and without co-administration of daily doses of obicetrapib tablets.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M1S 3V6
      • PharmaMedica Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy, non-smoking, male and female subjects, from 18 to 65 years of age.
• BMI ≥18.5 and ≥30 kg/m2
• Females may be of childbearing or non-childbearing potential. Childbearing potential (physically capable of becoming pregnant). Non-childbearing potential: Surgically sterile (i.e., both ovaries removed, uterus removed, or bilateral tubal ligation); and/or postmenopausal (no menstrual period for at least 12 consecutive months without any other medical cause and FSH and LH values consistent with being postmenopausal).
• Willing to use acceptable, effective methods of contraception.
• Able to tolerate venipuncture.
• Be informed of the nature of the study and give written consent prior to any study procedure.

Exclusion Criteria:

• History of clinically significant neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• Known or suspected carcinoma.
• History of hypersensitivity or idiosyncratic reaction to obicetrapib, ezetimibe, or any other drug substances with similar activity.
• History of clinically significant angioedema.
• History of myopathy, rhabdomyolysis, or myalgia, which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• History of pancreatitis, which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• History of severe cutaneous adverse reactions (SCARs), Steven-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilic and systemic symptoms (DRESS), which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• Presence of hepatic or renal dysfunction.
• History of malabsorption within the last year or presence of clinically significant gastrointestinal (GI) disease.
• Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption.
• History of drug or alcohol addiction requiring treatment.
• Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
• Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) or urine cotinine.
• Difficulty fasting or consuming standard meals.
• Use of tobacco or nicotine-containing products within six (6) months prior to the first drug administration.

• Females who:

  • Have used implanted, injected, intravaginal, or intrauterine hormonal contraceptives within six (6) months prior to the first drug administration;
  • Have used oral or transdermal hormonal contraceptives within 21 days prior to the first drug administration;
  • Are pregnant (serum β-hCG consistent with pregnancy); or
  • Are breast-feeding.

• Donation or loss of whole blood (including clinical trials):

  • ≥50 mL and <500 mL within 30 days prior to the first drug administration; or
  • ≥500 mL within 56 days prior to the first drug administration.
• Participation in a clinical trial that involved administration of an investigational medicinal product within 30 days prior to the first drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results.
• On a special diet within 30 days prior to the first drug administration (e.g., liquid, protein, raw food diet).
• Have had a tattoo or body piercing within 30 days prior to the first drug administration.
• Have clinically significant findings in vital signs measurements.
• Have clinically significant findings in a 12-lead ECG.
• Have clinically significant abnormal laboratory values.
• Have significant diseases.

• Use of any of the following within 30 days prior to drug administration:

  • Bile acid sequestrant (e.g., cholestyramine)
  • Cyclosporine
  • Digoxin
  • Drugs that alter GI pH/movement (e.g., omeprazole, ranitidine)
  • Enzyme-modifying drugs known to induce/inhibit hepatic drug metabolism
  • Fibrates (e.g., fenofibrate)
  • Gemfibrozil
  • Glipizide
  • Inducers and inhibitors of breast cancer resistant protein
  • Inducers and inhibitors of CYP3A4
  • Inducers and inhibitors of OATP1B1/OATP1B3
  • Inducers and inhibitors of P-glycoprotein
  • Statin
  • Warfarin
• Have clinically significant findings from a physical examination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: obicetrapib with and without co-administration of ezetimibe; Ezetimibe 10mg tablets daily from Days 1-17 plus obicetrapib 10mg tablets on Day -9 and Day 8	Drug: Obicetrapib 10mg; tablets; Drug: Ezetimibe 10mg; tablets
Active Comparator: ezetimibe with and without co-administration of obicetrapib; Obicetrapib 10mg tablets daily from Days 1-15 plus ezetimibe10mg tablets on Day -3 and Day 12	Drug: Obicetrapib 10mg; tablets; Drug: Ezetimibe 10mg; tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	Maximum measured analyte concentration	time zero (0) to the time of the last measurable analyte concentration (t), up to 18 days
AUCt (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	The area under the analyte concentration versus time curve	time zero (0) to the time of the last measurable analyte concentration (t)
AUCinf (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	The area under the analyte concentration versus time curve	m time zero to infinity

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	Time of the maximum measured analyte concentration	zero (0) to the time of the last measurable analyte concentration (t), up to 18 days
Kel (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	The apparent first-order elimination rate constant	time zero (0) to the time of the last measurable analyte concentration (t), up to 18 days
Thalf (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	The apparent elimination half-life	zero (0) to the time of the last measurable analyte concentration (t), up to 18 days
CL/F (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	Total body clearance	time zero (0) to the time of the last measurable analyte concentration (t), up to 18 days
Vd/F (Obicetrapib, unconjugated ezetimibe, and ezetimibe glucuronide)	Apparent volume of distribution	time zero (0) to the time of the last measurable analyte concentration (t), up to 18 days

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma
• Collaborators: Pharma Medica Research, Inc.
• Investigators: Principal Investigator: Mark M Feldman, Pharma Medica Research, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): November 12, 2024
• Study Completion (Actual): November 12, 2024

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: TA-8995-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No