A Single Ascending Dose Escalation Clinical Trial to Investigate Safety and Pharmacokinetics of VVZ-149 Injection in Healthy Older Male Volunteers
Overview
- Phase
- Phase 1
- Intervention
- VVZ-149 injection
- Conditions
- Healthy
- Sponsor
- Vivozon, Inc.
- Enrollment
- 24
- Primary Endpoint
- Dose-limiting toxicity and maximum tolerated dose
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The objective of this study is to investigate the safety, tolerability and pharmacokinetics (PK) of VVZ-149 injection after a single dose or loading/maintenance dose in healthy older male volunteers.
Detailed Description
VVZ-149 injection, an investigational product (IP) in this clinical study, is a multi-target analgesic drug candidate against glycine transporter type II (GlyT2) and serotonin receptor 2A (5HT2A). The target receptors have been known to play important roles in the induction and transmission of pain signals in the pain-related neural system. There have been efforts to develop new drugs that selectively antagonize the GlyT2 or 5HT2A, but it was unsuccessful due to limitations of single-target drugs. VVZ-149 showed morphine-comparable analgesic and gabapentin-comparable anti-allodynic effects in various rat models of pain.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who voluntarily agree to participate and sign an IRB-approved informed consent form (ICF) prior to receiving any of the screening procedures
- •Healthy male subjects aged between 50-84, inclusive at screening (the subjects aged 65 years or over can participate only in the single dose trial)
- •Subjects with body weights between 50-90 kg, inclusive and with body mass index (BMI) between 18.0-29.9 kg/m2, inclusive
- •Healthy subjects satisfying eligibility at screening (medical histories, physical examination, vital sign, electrocardiogram (ECG), hematology, clinical chemistry and urinalysis)
- •Subjects who willing to use an medicinal allowed method of contraception or sterility during the study period
Exclusion Criteria
- •Subjects who have a presence or history of clinically significant hepatic, renal, neurologic, immunologic, pulmonary, endocrine, hematological, neoplastic, cardiovascular or psychiatric (e.g. mood disorders or obsessive-compulsive disorder) diseases (subjects with currently well-controlled conditions including hypertension, hyperlipidemia, arthritis, prostatic hypertrophy and cataracts may allow to participate at the discretion of the investigator.)
- •Subjects with chronic infection or meaningful acute infection
- •Subjects who have a history of clinically significant hypersensitivities or hypersensitivities to the ingredient of same family with IP and other drug (e.g. aspirin and antibiotics)
- •Subjects who have a family history of chronic pain or with a first-degree relative with chronic pain
- •Subjects who have a clinically significant ECG abnormalities or QTc interval \>450 ms
- •Subjects who meet the following criteria at screening:
- •AST or ALT level \> 3 times the upper limit of the normal range
- •Calculated eGFR by MDRD equation \< 60 ml/min
- •Platelets ≤ 75,000/mm3, Hemoglobin ≤ 9 g/dL, Neutrophils absolute ≤ 1000/mm3
- •Subjects who show the following vital signs at the screening:
Arms & Interventions
Single Dose_VVZ-149 injection
1. Cohort A (50-64 years old), Cohort B (65-84 years old) 2. For 2.5, 5mg/kg 3. 4-hr intravenous infusion of VVZ-149 injection 4. 6 subjects will be administered within each age group. Total 24 subjects will participate.
Intervention: VVZ-149 injection
Loading/Maintenance_VVZ-149 injection
1. Cohort A (50-64 years old) This trial is conducted only in the Cohort A one week after the single IV infusion. 2. For Loading + Maintenance dose: 0.75 mg/kg+ 0.55 mg/kg/h, 1.5 mg/kg + 1.10 mg/kg/h 3. intravenous infusion 4. 4 subjects will be randomly assigned within each dose group, respectively. Total 8 subjects will participate.
Intervention: VVZ-149 injection
Loading/Maintenance_Placebo
1. Cohort A (50-64 years old) 2. For Loading + Maintenance dose: 0.75 mg/kg+ 0.55 mg/kg/h, 1.5 mg/kg + 1.10 mg/kg/h 3. intravenous infusion 4. 2 subjects will be randomly assigned within each dose group, respectively. Total 4 subjects will participate.
Intervention: Placebo
Outcomes
Primary Outcomes
Dose-limiting toxicity and maximum tolerated dose
Time Frame: 8 day
Any Common Toxicity Criteria for Adverse Effects grade 3 or more adverse event , All significant toxicity judged by the investigator
Secondary Outcomes
- Safety and Tolerability as measured by Adverse event, physical examination, vital signs, 12-lead ECG, consecutive ECG, SpO2 monitoring and Clinical laboratory.(8 day)