Phase I Study to Investigate Safety, Tolerability, and Pharmacokinetics of VVZ-149 Injection

NCT01905410 | Completed Phase 1

• 1 other identifier: PT-VVZ149-01
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

VVZ-149 is a novel analgesic drug candidate that shows a potential analgesic activity inhibiting GlyT2 and 5HT2A simultaneously. There have been many efforts to develop single-target selective drugs to treat pain, but usually unsuccessful due to the lack of efficacy or limitations of single-target approach for new drug discovery. VVZ-149 is expected to have a dual-target activity, demonstrated having a synergism between GlyT2 and 5HT2A antagonistic activities to maximize an antinociceptive effect in the in vivo animal models. Now the investigators are developing VVZ-149 as an IV injection to treat post-operative pain. The primary objective of this study is to evaluate a safety, tolerability and pharmacokinetic properties of VVZ-149 injection with placebo in healthy male volunteers. This Phase 1 study consists of a randomized, double-blind, placebo controlled, single and multiple ascending dose (SAD \& MAD) escalation clinical trials.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Assessment of Adverse Events Appearance According to the NCI CTCAE V 4.02

  According to the NCI CTCAE V 4.02, DLT (Dose Limiting Toxicity) is defined when it is applicable at least one criterion among following items * adverse event over CTCAE Grade 3 * Any other significant toxicity according to the investigator's judgment Safety and Tolerability Measurements : physical examination, vital signs, 12-lead ECG, consecutive ECG and SpO2 monitoring, clinical laboratory tests(hematology, clinical chemistry, liver function, thyroid function, coagulation, urine analysis)

  upto 8 days (SAD) / 13 days (MAD)

Secondary Outcomes (1)

• Pharmacokinetic parameters

  upto 2 days (SAD) / 5 days (MAD)

Study Arms (4)

single treatment - VVZ-149 Injection

EXPERIMENTAL

single ascending dose escalation * 0.25, 0.5, 1, 2, 4, 6, and 8 mg/kg Cohorts * 4 hours IV infusion

Drug: VVZ-149 Injection

single treatment - placebo

PLACEBO COMPARATOR

* The matching volume of placebo (water for injection) to each experimental cohort * 4 hours IV infusion

Drug: placebo

multiple treatment - VVZ-149 Injection

EXPERIMENTAL

Based on the results of SAD trials, low and high dosage are determined for MAD trials. * high and low dosage * 4 hours IV infusion x 2 times/day x 3 days

Drug: VVZ-149 Injection

multiple treatment - placebo

PLACEBO COMPARATOR

* The matching volume of placebo (water for injection) to each experimental cohort * 4 hours IV infusion x 2 times/day x 3 days

Drug: placebo

Interventions

VVZ-149 Injection DRUG

VVZ-149 in water for injection

Also known as: VVZ-149 Injection or Water for injection

multiple treatment - VVZ-149 Injection; single treatment - VVZ-149 Injection

placebo DRUG

water for injection

Also known as: VVZ-149 Injection or Water for injection

multiple treatment - placebo; single treatment - placebo

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• willingness to sign the written informed consent form (ICF)
• \~45 years, inclusive, healthy male
• \~90kg, inclusive, and within the 20% of ideal body weight
• compatible at screening ( medical history, physical examination, vital signs, ECG, haematology, clinical chemistry, urinalysis)
• sterility or keep an ascetic life or male subjects and their female sexual partners had to use a following contraception method during the study period \*the medical contraception permissible method: condom, at least partner had to take the oral contraceptive over the 3 months or had to use the injection or insertion contraceptives, intrauterine device.

You may not qualify if:

• Presence or history of diseases or abnormalities of liver, kidney, nervous system, respiratory system, endocrine system, or cardiovascular system. Presence or history of hemopathy or psychopathy (mood disorder, obsessive compulsive disorder etc.) Carrier of hepatitis virus in content of the liver disease, exclusive
• History of hypersensitivity reactions significant clinically or hypersensitivity reaction to the investigational product, the drugs containing identical ingredient, or other drugs (aspirin, antibiotic etc.)
• Family history of significant chronic pain disease or case of the immediate family (parent or brother) with chronic pain disease
• Electrocardiogram QTc \> 430 ms, PR interval \> 200 msec, QRS interval \> 120 msec, or any other clinically significant opinion at screening, exclusive
• Any of following results in the Clinical laboratory at screening, exclusive
• Exceed 1.25 times of the upper limit of the normal range of AST,AST
• Exceed 1.5 times of the upper limit of the normal range of BUN, Cr
• Out of normal range in Thyroid function (TSH, T4, FT4, T3) parameters
• Abnormal blood pressure (systolic \> 150 mmHg or \< 90 mmHg, diastolic \> 95 mmHg or \< 60 mmHg) in vital signs at screening, exclusive
• history of drug abuse, positive screen on the an alcohol breath test and an urine drug screening
• Taking any ETC or oriental medicine within 2 weeks prior to drug administration, taking any OTC or vitamins within a week prior to drug administration, (but could participate in the study if other conditions are considered appropriate by the medical investigator)
• Participation in a drug study (clinical trials) within 2 months prior to drug administration
• Donation of whole blood within 2 months or blood component within a month or receiving a blood transfusion within a month prior to drug administration
• Intake of more than 21 units per week (one unit of alcohol (10 g of pure alcohol) equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits), Unable to stop drinking during the study period
• A smoker (if case of non-smoker to stop smoking within 3 months prior to drug administration, they could participate in this study) and positive screen on urine cotinine test.

Sponsors & Collaborators

• Vivozon, Inc.: lead

Study Sites (1)

Seoul National University Bundang Hospital

Sungnam-Si, Gyeonggi-do, 463-707, South Korea

Location

MeSH Terms

Interventions

Water; Injections

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jae Yong Chung, MD, PhD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: July 23, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: April 1, 2014
• Last Updated: March 13, 2019

Record last verified: 2013-07

Locations

KR (1)