Multiple Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY03005

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY03005

Objectives

• To evaluate the safety and tolerability of escalating multiple oral doses of LY03005 in healthy subjects.
• To characterize the pharmacokinetics of escalating multiple oral doses of LY03005.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder, Recurrent, Unspecified
• Intervention / Treatment: Drug: Placebo; Drug: LY03005

Detailed Description

This will be a randomized, double-blind, placebo-controlled, multiple ascending dose study to be conducted in the US. Approximately 48 healthy subjects will be enrolled into one of the four groups

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Are capable of giving informed consent and complying with study procedures;
2. Are between the ages of 18 and 45 years, inclusive;

3. A negative pregnancy test result prior to screening and admission for all female subjects, and meet the following criteria defined as:

   1. If child-bearing potential, agree to avoid pregnancy during the study and one month after the end of the study by using effective contraceptive method(s), such as an intrauterine device (IUD), diaphragm with spermicide, and condoms with spermicide.
   2. Surgically sterile for at least 3 months prior to screening
   3. Postmenopausal
4. Considered healthy by the Principal Investigator, based on a detailed medical history, full physical examination, clinical laboratory tests, 12-lead ECG and vital signs;
5. Nonsmoker, defined as not having smoked or used any form of tobacco in more than 6 months before screening;
6. Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 50 kg;
7. Willing and able to adhere to study restrictions and to be confined at the clinical research center.

Exclusion Criteria:

Subjects will be excluded from study entry if any of the following exclusion criteria are present at screening or admission:

1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity;
2. Subjects with a mean systolic blood pressure of three measurements less than 130 mmHG, or a mean diastolic blood pressure of three measurements less than 90 mmHG at screening. Blood pressure will be measured at supine position.
3. Known or suspected malignancy;
4. Positive blood screen for human immunodeficiency virus (HIV), or hepatitis B surface antigen (HBsAg), or hepatitis C virus;
5. A history of seizure. However, a history of febrile seizure is allowed;
6. Positive pregnancy test result, or plan to become pregnant if female;
7. A hospital admission or major surgery within 30 days prior to screening;
8. Participation in any other investigational drug trial within 30 days prior to screening;
9. DSM-V substance use disorder within 6 months prior to screening;
10. A positive result for alcohol or drugs of abuse at screening or admission;
11. Tobacco use within 6 months prior to screening;
12. An unwillingness or inability to comply with food and beverage restrictions during study participation;
13. Donation or blood collection of more than 1 unit (approximate 450 mL) of blood (or blood products) or acute loss of blood during the 90 days prior to screening;
14. Use of prescription or over-the-counter (OTC) medications, and herbal medicines (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);
15. A history of intolerance or hypersensitivity to venlafaxine or desvenlafaxine or any excipients;
16. A 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; 17 An unwillingness of male participants to use appropriate contraceptive measures if engaging in sex intercourse with a female partner of childbearing potential. Appropriate measures include use of a condom and spermicide and, for female partners, use of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, progesterone sub-dermal implants, or a tubal ligation. Sexual intercourse with pregnant or lactating women is prohibited.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LY03005; LY03005 40, 80, 120, or 160 mg	Drug: LY03005; LY03005 is a new investigational pro-drug of desvenlafaxine formulated as extended-release oral tablets for the treatment of major depressive disorder.; Other Names: 4-Methylbenzoate of desvenlafaxine hydrochloride
PLACEBO_COMPARATOR: Placebo; Placebo at 40, 80, 120, or 160 mg	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Safety and Tolerability of LY03005	3 to 4 months

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Investigators: Principal Investigator: David Krefetz, MD, PRA - CRI Lifetree

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): March 1, 2015

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 21, 2014
• First Posted (ESTIMATE): October 22, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): October 21, 2015
• Last Update Submitted That Met QC Criteria: October 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; 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 MAD; LY03005/CT-USA-102 (OTHER: Luye)