A Relative Bioavailability Food Effect Study of LY03005

A Randomized, Open-Label, 2-Period, Crossover Trial to Assess the Relative Bioavailability of 80 mg LY03005 After Single Dose Administration to Healthy Subjects Under Fed Versus Fasted Conditions

The objective if this study is to assess the relative bio-availability of single oral doses of 80 mg LY03005 tablets administered to healthy subjects under fed versus fasted conditions in a 2-period, crossover trial.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: LY03005

Detailed Description

Thirty-two (32) eligible healthy subjects between ages of 18-50 years old will be enrolled and randomized to either Sequence 1 (fed to fasted state) versus Sequence 2 (fasted to fed state) at a 1:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pharmaron CPC, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Capable of giving informed consent and complying with trial procedures;
2. Male and female subjects between the ages of 18 and 50 years, inclusive;
3. Considered healthy by the Investigator based on a detailed medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
4. Nonsmoker, defined as not having smoked or used any form of tobacco for at least 6 months before Screening based on subject report;
5. Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight >/= 50 kg;
6. Willing and able to adhere to trial procedures and to be confined at the clinical research unit (CRU).
7. All female subjects (childbearing potential and non-childbearing potential) must have a negative serum pregnancy test result at Screening. In addition, female subjects must meet 1 of the following 3 conditions: (a) postmenopausal for at least 12 months without an alternative medical cause, (ii) surgically sterile (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal occlusion) based on subject report, or (iii) if of childbearing potential and heterosexually active, practicing or agree to practice a highly effective method of contraception. Highly effective methods of birth control include an intrauterine device (IUD), intrauterine hormone-releasing system (IUS), and contraceptives (oral, skin patches, or implanted or injectable products) using combined or progestogen-only hormonal contraception associated with inhibition of ovulation. A vasectomized male partner is an acceptable birth control method if the vasectomized partner is the sole sexual partner of the female subject and the vasectomized partner has received medical confirmation of surgical success. Highly effective methods of birth control must be used for at least 14 days prior to study drug dosing, through the end of study (EOS) visit or early termination, and for a minimum of 1 month after the last dose of study drug to minimize the risk of pregnancy. Sexually active, fertile, male subjects must be willing to use acceptable contraception methods (such as double-barrier methods of a combination of male condom with either cap, diaphragm, or sponge with spermicide) from the first dose of study drug through the EOS visit or early termination, and for a minimum of 1 month after the last dose of study drug.

Exclusion Criteria:

1. Clinically significant past medical history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric (including life-long history of depression and/or anxiety), renal, hepatic, bronchopulmonary, neurologic, immunologic, ophthalmological, or lipid metabolism disorders; or drug hypersensitivity; or any condition that in the judgement of the Investigator will affect the trial results or the subject's safety;
2. History of suicide attempt in the past 12 months and/or seen by the Investigator as having a significant history of risk of suicide or homicide;
3. History or presence of malignancy other than adequately treated and cured basal cell skin cancer, squamous cell skin cancer, or in-situ cervical cancer, within 5 years prior to screening;
4. Clinically relevant illness within 1 month prior to Screening or at Screening that may interfere with the conduct of this trial;
5. Medically uncontrolled high blood pressure with mean systolic blood pressure >140 mmHg or mean diastolic blood pressure >90 mmHg at Screening after 3 measurements (after at least 5 minutes of rest in a seated position);
6. History of Long QT Syndrome (LQTS) or a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
7. Positive blood screen for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
8. History of seizure (history of febrile seizure allowed);
9. Hospital admission or major surgery within 30 days prior to Screening;
10. Participation in any other investigational drug trial within 30 days prior to Screening;
11. History of prescription drug abuse or illicit drug use within 6 months prior to Screening;
12. History of alcohol abuse according to medical history within 6 months prior to Screening;
13. Positive screen for alcohol and/or drugs of abuse;
14. Tobacco use within 6 months prior to Screening based on subject report or positive nicotine screen;
15. History of intolerance or hypersensitivity to ODV or medicines containing ODV or its precursor venlafaxine;
16. Participation in a previous clinical trial of either LY03005 or ODV or medicines containing ODV or its precursor, venlafaxine, within 30 days prior to Screening;
17. Unwillingness or inability to comply with food and beverage restrictions during trial participation;
18. Donation of blood of more than 1 unit (approximate 450 mL) or blood products or acute loss of blood during the 90 days prior to Screening;
19. Use of prescription or over-the-counter (OTC) medications and herbals (including St John's Wort, herbal teas, garlic extracts) within 14 days prior to dosing (Note: Use of acetaminophen at <3g/day is permitted until 24 hours prior to dosing).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence 1: LY03005 Fed Crossover to Fasted; Sequence 1 will receive a single oral dose of LY03005 (80 mg) under fed conditions in Treatment Period 1 and a single oral dose of LY03005 (80 mg) under fasted conditions in Treatment Period 2.	Drug: LY03005; 80 mg oral tablet single dose; Other Names: Desvenlafaxine
EXPERIMENTAL: Sequence 2: LY03005 Fasted Crossover to Fed; Sequence 2 will receive a single oral dose of LY03005 (80 mg) under fasted conditions in Treatment Period 1 and a single oral dose of LY03005 (80 mg) under fed conditions in Treatment Period 2.	Drug: LY03005; 80 mg oral tablet single dose; Other Names: Desvenlafaxine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameters	Area under the concentration-time curve (AUC)	PK samples drawn at predose (within 30 minutes prior to dosing) and at 1, 2, 3, 4 (±5 minutes), 6, 8, 10, 12, 16, 24, 32, 48, and 72 hours (±15 minutes) after the dose.
Pharmacokinetic Parameters	Maximum concentration (Cmax) for the Pharmacokinetics (PK) of O-desmethyl-venlafaxine (ODV) from LY03005	PK samples drawn at predose (within 30 minutes prior to dosing) and at 1, 2, 3, 4 (±5 minutes), 6, 8, 10, 12, 16, 24, 32, 48, and 72 hours (±15 minutes) after the dose.

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Investigators: Study Director: Kevin Booth, MD, DVM, Luye Pharma.

Publications and helpful links

Helpful Links

• U.S. FDA Resources
• Drug information
• Desvenlafaxine
• Desvenlafaxine Succinate

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 16, 2019
• Primary Completion (ACTUAL): February 16, 2019
• Study Completion (ACTUAL): February 16, 2019

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (ACTUAL): January 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Mood Disorders; Depressive Disorder; Physiological Effects of Drugs; Mental Disorders; Depressive Disorder, Major; Antidepressive Agents; Psychotropic Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin and Noradrenaline Reuptake Inhibitors; Membrane Transport Modulators; Neurotransmitter Uptake Inhibitors; Desvenlafaxine Succinate
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: LY03005/CT-USA-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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