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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.
Shock is a condition of reduced tissue perfusion, resulting in the inadequate delivery of oxygen and nutrients that are necessary for cellular function. Common causes of shock are hypovolemia (excessive blood or fluid loss), sepsis, cardiac failure, dengue and neuroendocrine dysfunction. The current resuscitative measures include administration of crystalloid solutions (e.g., 0.9% saline, Ringer's lactate, or hypertonic saline) or colloid solutions (e.g., hydroxyethyl starch, albumin, or dextrans). These 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. Successful completion of phase I studies will lead to efficacy studies in patients with hypovolemic shock.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| 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) |
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| 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) |
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| 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) |
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| 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 |
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| 3 doses equivalent to 2*MTD of PMZ-2010 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of pharmacokinetics of PMZ-2010 in plasma | Maximum concentration (Cmax), Time of maximum plasma concentration (Tmax), Area under the concentration-time curve (AUC) from time of dosing to the last quantifiable concentration (AUClast), Terminal elimination half-life (t½), Clearance (CL/F), Apparent volume of distribution during the terminal elimination phase (Vz/F) of PMZ-2010 in plasma after single ascending doses. |
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Inclusion Criteria: Subjects to be enrolled in this trial must fulfill all of these criteria:
Exclusion Criteria: Subjects meeting any of these criteria will not be enrolled in the study:
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| Name | Affiliation | Role |
|---|---|---|
| Ashish O Goyal, MD | Jehangir Clinical Development Centre Pvt. Ltd. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jahangir Clinical Development Centre Pvt. Ltd. | Pune | Maharashtra | Pune 411001 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23871440 | Background | 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. | |
| 22964270 | 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. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jun 19, 2018 | |
| Reset | Dec 27, 2018 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 19, 2018 | Dec 27, 2018 |
| ID | Term |
|---|---|
| C045913 | centhaquine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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Three equally divided doses (total dose/day equivalent to 2*MTD) of PMZ-2010 (n=3) or placebo (n=1) for 2 days |
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| 24 hours |
| Phamacodynamics profile of PMZ-2010 | Change in systolic and diastolic blood pressure, pulse rate, heart rate, QTcF after single ascending dose and multiple ascending doses | 7 days |
| 22487389 | 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. |