A Bioavailability Study of NALDEBAIN ER Injection and Nalbuphine Injection in Healthy Volunteers.

NCT04256434 | Completed Phase 1 FDA Drug

• 1 other identifier: LT1001-104
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, sequential 2 cohort, intramuscular injection study in healthy volunteers. The study will enroll approximately 24 healthy volunteers to examine the safety, pharmacokinetics, and bioavailability after intramuscular injection of NALDEBAIN ER Injection and nalbuphine injection.

Conditions

Health

Outcome Measures

Primary Outcomes (1)

• Bioavailability of nalbuphine after intramuscular injection of NALDEBAIN and Nalbuphine.

  To evaluate the relative bioavailability of nalbuphine after intramuscular injection of NALDEBAIN and Nalbuphine.

  Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing.

Secondary Outcomes (9)

• Maximum plasma concentration (Cmax) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate.

  Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing.

• Tmax of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate.

  Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing.

• AUCinf of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate.

  Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing.

• AUClast of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate.

  Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing.

• Elimination half-life (t1/2) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate.

  Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing.

Study Arms (2)

Dinabuphine sebacate

EXPERIMENTAL

Each subject in cohort 1 will receive 150 mg Dinalbuphine sebacate (75 mg/mL x 2 mL) intramuscularly.

Drug: Dinalbuphine sebacate

Nalbuphine HCl

ACTIVE COMPARATOR

Each subject in cohort 2 will receive 20 mg Nalbuphine (20 mg x 1 mL) intramuscularly.

Drug: Nalbuphine HCl

Interventions

Dinalbuphine sebacate DRUG

150 mg Dinalbuphine sebacate

Also known as: NALDEBAIN ER Injection, Sebacoyl Dinalbuphine Ester Injection, LT1001

Dinabuphine sebacate

Nalbuphine HCl DRUG

20 mg Nalbuphine

Also known as: Nalbuphine HCl Injection

Nalbuphine HCl

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, 18 to 55 years of age inclusive at the time of signing the informed consent form
• Body weight must be above 60 kg.
• Body Mass Index (BMI) 18 to 40 kg/m2
• In good health on the basis of medical history, physical examination, electrocardiogram, chest X-ray, and routine laboratory evaluations.
• If male, must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period until the final PK sample, and refrain from donating sperm for 90 days after the dosing.
• If female, is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period until the last PK sample.
• Vital signs (after 3 minutes resting in a semi-supine position) which are within the following ranges:
• Oral temperature between 35.0-37.5°C.
• Systolic blood pressure, 90-140 mm Hg.
• Diastolic blood pressure, 50-90 mm Hg.
• Pulse rate, 50-90 bpm.
• Respiratory rate, 12-20 bpm
• Oxyhemoglobin saturation, ≥95%
• Fasting blood glucose, \<110 mg/dL.

You may not qualify if:

• Use of any prescription medications or over-the-counter, non-prescription preparations (including herbal preparations) within 2 weeks prior to study entry unless deemed acceptable by the Investigator (except up to 5 doses of ≤ 1000 mg of acetaminophen or ≤ 400 mg ibuprofen within this 2 weeks period).
• Alcohol or caffeine ingested within 72 hours prior to dosing.
• Significant illness within 2 weeks prior to dosing.
• Participation in any clinical investigation within 2 months prior to dosing or longer as required by local regulation.
• Donation or loss of more than 500 mL of blood within 3 months prior to dosing. Donation or loss of more than 250 mL of blood within 2 months prior to dosing.
• Documented history of cardiovascular disease.
• Documented history of gastrointestinal disease.
• Documented history of asthma or lung disease.
• Presence of liver disease or liver injury as indicated by an abnormal liver function profile such as aspartate aminotransaminase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), Alkaline Phosphatase, or Total Bilirubin at Screening. (value of AST or ALT above 3 times of the upper limit of the normal range; other items clinically significant abnormality judged by investigator).
• Presence of impaired renal function as indicated by abnormal creatinine or BUN values or abnormal urinary constituents at Screening. (value of creatinine or BUN beyond the range from -20% of the lower limit of the normal range to +20% of the upper limit of the normal range; other items clinically significant abnormality judged by investigator)
• Documented history of neurological disease.
• Documented history of psychiatric disease.
• Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV; has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or tests positive for HBsAg or anti-HCV at Screening.
• A known hypersensitivity to nalbuphine or its analogs.
• History of drug or alcohol abuse within 12 months prior to dosing or positive test results for alcohol or drugs of abuse at Screening and admission.

Sponsors & Collaborators

• Lumosa Therapeutics Co., Ltd.: lead

Study Sites (1)

WCCT Global Inc.

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

sebacoyl dinalbuphine ester; Nalbuphine

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• David Nguyen, MD

  WCCT Global

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, sequential 2 cohort, intramuscular injection study in healthy volunteers.

Study Record Dates

• First Submitted: February 2, 2020
• First Posted: February 5, 2020
• Study Start: January 31, 2020
• Primary Completion: May 29, 2020
• Study Completion: May 29, 2020
• Last Updated: November 19, 2021

Record last verified: 2021-11

Locations

US (1)