A Study to Determine the Safety, Tolerability and Pharmacokinetics of PMZ-2010 (Centhaquin) in Healthy Volunteers

NCT02408731 | Completed Phase 1 DMC

• 1 other identifier: CT-430-CENT-2012
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Shock is a condition of reduced tissue perfusion, resulting in the inadequate delivery of oxygen and nutrients that are necessary for cellular function. The current resuscitative agents can extend patient's life to a limited extent. Centhaquin (PMZ-2010) in very low doses reduced blood lactate levels, improved blood pressure, cardiac output, survival and proved to be a highly effective resuscitative agent. The investigators are conducting a phase I clinical study in humans to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of centhaquin citrate in normal healthy volunteers.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Measure blood pressure, heart rate, body temperature, ECG, laboratory parameters and clinical assessment.after single and multiple ascending doses of PMZ-2010.

  7 days

Secondary Outcomes (2)

• Composite of pharmacokinetics of PMZ-2010 in plasma

  24 hours

• Phamacodynamics profile of PMZ-2010

  7 days

Study Arms (6)

Single dose of 0.005 mg/kg of PMZ-2010

EXPERIMENTAL

A single dose of 0.005 mg/kg of PMZ-2010 (n=3) or placebo (n=1)

Drug: PMZ-2010 (Centhaquin)

Single dose of 0.01 mg/kg of PMZ-2010

EXPERIMENTAL

A single dose of 0.01 mg/kg of PMZ-2010 (n=3) or placebo (n=1)

Drug: PMZ-2010 (Centhaquin)

Single dose of 0.05 mg/kg of PMZ-2010

EXPERIMENTAL

A single dose of 0.05 mg/kg of PMZ-2010 (n=3) or placebo (n=1)

Drug: PMZ-2010 (Centhaquin)

Single dose of 0.10 mg/kg of PMZ-2010

EXPERIMENTAL

A single dose of 0.10 mg/kg of PMZ-2010 (n=3) or placebo (n=1)

Drug: PMZ-2010 (Centhaquin)

3 doses equivalent to MTD of PMZ-2010

EXPERIMENTAL

Three equally divided doses (total dose/day equivalent to MTD) of PMZ-2010 (n=3) or placebo (n=1) for 2 days

Drug: PMZ-2010 (Centhaquin)

3 doses equivalent to 2*MTD of PMZ-2010

EXPERIMENTAL

Three equally divided doses (total dose/day equivalent to 2\*MTD) of PMZ-2010 (n=3) or placebo (n=1) for 2 days

Drug: PMZ-2010 (Centhaquin)

Interventions

PMZ-2010 (Centhaquin) DRUG

As per the randomization schedule, injection of PMZ-2010 or placebo (100 ml normal saline) will be administered to each subject under supervision of investigator as an intravenous infusion over one hour. PMZ-2010 will be dissolved in normal saline (100 ml) before administration.

Also known as: Placebo (normal saline)

3 doses equivalent to 2*MTD of PMZ-2010; 3 doses equivalent to MTD of PMZ-2010; Single dose of 0.005 mg/kg of PMZ-2010; Single dose of 0.01 mg/kg of PMZ-2010; Single dose of 0.05 mg/kg of PMZ-2010; Single dose of 0.10 mg/kg of PMZ-2010

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sex: male
• Age: 18-60 yr old, both inclusive
• Having a Body Mass Index (BMI) between 18.5-28 kg / m2 (both inclusive) and body weight not less than 45 kg
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; and to comply with the requirements of the entire study
• Voluntarily given written informed consent to participate in this study
• Be of normal health as determined by the principal investigator from medical history, physical examination and laboratory investigations, 12-lead ECG and X-ray chest of the subjects performed within 10 days prior to the admission of the study
• Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, coke, chocolate, "power drinks") and grapefruit (juice) from 48 h prior to each admission until study completion

You may not qualify if:

• Employees of JCDC or Pharmazz India Private Limited
• Not willing to use contraceptives (preferably condoms) during sexual activity for the period of 3 months from the date of check-in
• History of hypersensitivity and / or intolerance to Centhaquin or any other related compounds.
• History of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study.
• Clinically abnormal ECG and Chest X-ray.
• Physical findings: clinically relevant abnormal physical findings (including body temperature) suggesting underlying pathologies or those which could interfere with the objectives of the study.
• Subjects with impaired renal function as measured by glomerular filtration rate \<90 mL/min/1.73m2 estimated using the modification of diet in renal disease (MDRD) formula \[GFR for Male =186 × (Serum Creatinine)-1.154 × Age-0.203 \]12
• Laboratory values that are significantly different than the normal reference range and/or are deemed to be of clinical significance by the investigator
• Presence of reactive disease markers of HIV 1 and II, HBsAg, HCV or VDRL.
• Positive for alcohol breath test and/or urine drug screen (barbiturates, benzodiazepines, amphetamine, cocaine, opiates, tetra-hydro cannabinol).
• Any evidence of organ dysfunction or any clinically significant deviation from the normal, in physical or clinical determinations.
• Diseases: relevant history of renal, hepatic, cardiovascular, respiratory, skin, haematological, endocrine, neurological or gastrointestinal diseases. History of depression, psychosis, schizophrenia or any other severe psychiatric diseases, or epilepsy, or any other illness that may interfere with the aim of the study. History of any significant illness in the 4 weeks preceding the screening
• Medications: history of intake of any medications including over the counter medications (OTC) and any herbal agents at least 4 weeks period prior to study drug administration.
• Investigational drug trials: participation in the evaluation of any drug in the 3 months prior to the start of the study (dosing with IMP).
• Blood donation: Subjects who, through completion of this study, would have donated and/or lost more than 300 mL of blood in the past 12 weeks Note: In case the blood loss is ≤ 200 mL; subject may be dosed 60 days after blood donation or last sample of the previous study

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Study Sites (1)

Jahangir Clinical Development Centre Pvt. Ltd.

Pune, Maharashtra, Pune 411001, India

Location

Related Publications (3)

• Gulati A, Zhang Z, Murphy A, Lavhale MS. Efficacy of centhaquin as a small volume resuscitative agent in severely hemorrhaged rats. Am J Emerg Med. 2013 Sep;31(9):1315-21. doi: 10.1016/j.ajem.2013.05.032. Epub 2013 Jul 19.

  PMID: 23871440 BACKGROUND

• Lavhale MS, Havalad S, Gulati A. Resuscitative effect of centhaquin after hemorrhagic shock in rats. J Surg Res. 2013 Jan;179(1):115-24. doi: 10.1016/j.jss.2012.08.042. Epub 2012 Sep 2.

  PMID: 22964270 BACKGROUND

• Gulati A, Lavhale MS, Garcia DJ, Havalad S. Centhaquin improves resuscitative effect of hypertonic saline in hemorrhaged rats. J Surg Res. 2012 Nov;178(1):415-23. doi: 10.1016/j.jss.2012.02.005. Epub 2012 Apr 2.

  PMID: 22487389 BACKGROUND

MeSH Terms

Interventions

centhaquine; Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ashish O Goyal, MD

  Jehangir Clinical Development Centre Pvt. Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2015
• First Posted: April 3, 2015
• Study Start: October 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 28, 2015

Record last verified: 2015-04

Locations

IN (1)