Safety, Tolerability and Pharmacokinetics of NCO-48 Fumarate in Healthy Subjects

NCT04309526 | Completed Phase 1 FDA Drug

• 1 other identifier: NCO48F-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to evaluate the safety and tolerability of single oral doses of NCO-48 Fumarate in healthy subjects. The secondary objectives are to evaluate the pharmacokinetic (PK) profile of NCO-48 Fumarate and its active metabolite, tenofovir (TFV), in healthy subjects following single oral doses and to evaluate the effect of food on the PK of a 30 mg dose of NCO-48 Fumarate in healthy subjects.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Severity of all Adverse Events graded according to the Common Terminology Criteria for Adverse Events (CTCAE)

  An adverse event is defined as any untoward medical occurrence in a clinic investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. The severity of all adverse events will be graded according to the CTCAE version 4.0 from dosing until 30 days post dose.

  30 days

Secondary Outcomes (4)

• NCO-48 Fumarate Area Under the Concentration-Time Curve (AUC)

  7 days

• NCO-48 Fumarate Maximum Plasma Concentration (Cmax)

  7 days

• TFV Area under the Concentration-Time Curve (AUC)

  7 days

• TFV Maximum Plasma Concentration (Cmax)

  7 days

Study Arms (2)

NCO-48 Fumarate

EXPERIMENTAL

NCO-48 Fumarate

Drug: NCO-48 Fumarate

Placebo

PLACEBO COMPARATOR

Placebo Comparator

Drug: Placebo

Interventions

NCO-48 Fumarate DRUG

NCO-48 Fumarate

NCO-48 Fumarate

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female subjects 21 to 65 years of age, inclusive.
• Female subjects of non-childbearing potential must be surgically sterile or postmenopausal, defined as spontaneous amenorrhea for at least 2 years with follicle-stimulating hormone (FSH) in the post-menopausal range at the Screening Visit.
• Sexually active female subjects of childbearing potential (ie, ovulating, pre-menopausal, and not surgically sterile) with male partners or sexually active male subjects with female partners must agree to use a medically accepted contraceptive regimen during their participation in the study and for 90 days after the last dose of study drug.
• Male subjects must agree to abstain from sperm donation through 90 days after administration of the last dose of study drug.
• Body mass index (BMI) within the range of 18.5 to 30.0 kg/m2, inclusive, and body weight \>45 kg.
• Able to communicate effectively with the study personnel.
• Generally good health based upon the results of medical history, physical examination, vital signs, laboratory profile, and a 12-lead ECG, as judged by the Investigator.
• Nonsmokers, defined as not having smoked in the past 3 months prior to study drug administration.
• Willing and able to understand and comply with study procedures and restrictions, including confinement to the study site and consumption of study meals, and provide written informed consent according to institutional and regulatory guidelines.
• Estimated glomerular filtration rate \>60 mL/min/1.73 m2 calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration formula.

You may not qualify if:

• Females who are pregnant or breastfeeding or planning to become pregnant during the study.
• History or presence of asthma or other clinically significant pulmonary disease, thyroid disease (hypo- or hyperthyroidism), hepatitis (except for resolved hepatitis A), or other liver disease.
• Have any disease or condition (medical or surgical) that, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous systems; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of study drug or would place the subject at increased risk.
• Liver transaminase levels (aspartate aminotransferase or alanine aminotransferase) \>10% of the upper limit of normal, or presence of other abnormal laboratory values which are considered clinically significant at the Screening Visit or admission to study site (Day -1).
• Positive screening for hepatitis B (hepatitis B surface antigen), hepatitis C (hepatitis C antibody), or HIV (anti-HIV-1/2).
• Has used any other investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug.
• Use of any of the following:
• Prescription drugs, other than topical products without significant systemic absorption, use of thyroid medication or hormone replacement therapy for at least 6 months, and hormonal contraceptives, within 14 days or 5 half lives (whichever is longer) prior to the first dose of study drug.
• Natural health products should be restricted within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• Over-the-counter products and non-prescription drugs other than topical products without significant systemic absorption and/or hormone replacement therapy, within 7 days prior to the first dose of study drug, with the exception of the use of acetaminophen, which is allowed up to 1 g daily up to 24 hours prior to admission to the study site, then prohibited until after the last protocol-specified blood sample.
• Depot injection or implant of any drug (other than hormonal contraceptives) within 3 months prior to the first dose of study drug.
• Substances known to be strong inhibitors or inducers of cytochrome P450 enzymes within 14 days prior to the first dose of study drug through the last study visit.
• Unwilling to refrain from consumption of alcohol within 48 hours prior to each dose administration and during any inpatient period.
• Positive urine drug screen, positive alcohol breath test, and/or positive cotinine test at the Screening Visit or upon admission to the study site.
• History of alcohol abuse within 1 year prior to the Screening Visit or regular use of alcohol within 6 months prior to the Screening Visit.

Sponsors & Collaborators

• Nucorion Pharmaceuticals, Inc.: lead
• Ligand Pharmaceuticals: collaborator
• Medpace, Inc.: collaborator

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Leela Vrishabhendra, MD

  Medpace Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 16, 2020
• Study Start: March 18, 2020
• Primary Completion: August 3, 2020
• Study Completion: October 13, 2020
• Last Updated: November 3, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)