PK Study to Evaluate the Effect of PLC on Healthy Chinese Subjects by Multiple-doses

An Open-label, Single Arm, Self-controlled Safety and Pharmacokinetics Study to Evaluate the Effect of Propionyl L-carnitine Hydrochloride on Healthy Chinese Subjects by Diet and Multiple-doses

The main objective is to evaluate the effect of Propionyl-L-Carnitine Hydrochloride on clinical pharmacokinetic characteristics and its effect of clinical pharmacokinetic characteristics and safety on healthy Chinese subjects to provide a basis for market authorization registration

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Diseases
• Intervention / Treatment: Drug: Propionyl-L-Carnitine Hydrochloride

Detailed Description

This is a single group subject, open-label, self-controlled, 3 periods, multi-doses administration trial. 12 Healthy Chinese volunteers satisfying inclusion criteria were enrolled with equal number of male and female. Each subject goes through a 7-day Run-in period to eliminate the remaining L-carnitine like substance in the food to ensure the baseline level of endougenous L-Carnitien is stable；In period III, during the first 4 days，all healthy subjects take oral Propionyl-L-Carnitine 1g twice daily; on day 5, all healthy subjects take oral Propionyl-L-Carnitine 1g during fasting.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sex: Male and female of same proportion. Healthy individuals.
• Age: 19 to 45. Similar age.
• Weight: All subjects need to weigh ≥50 kg. BMI within 19~24 kg/m2. Similar weight between subjects.；
• Blood pressure: SBP 90-139mmHg，DBP 60-89 mmHg；
• Subjects need to understand and agree before the start of trial and signed the informed consent form.
• Subjects have to be able to communicate with the investigator and comply with the trial protocol.

Exclusion Criteria:

Laboratory investigations:

• Any items of safety evaluation index baseline values considered to be clinically significant abnormal by the investigator before the study;
• Hepatitis B surface antigen positive;
• Hepatitis C antibody positive;
• HIV, Syphilis positive;
• During screening or 1st day of trial before drug administration, any ECG abnormality shown

Drug history:

• Taken any drugs that inhibit or induce hepatic metabolism of drug 1 month prior to the trial;
• Taken any drugs within 2 weeks prior to the trial (including prescription drugs, non-prescription drugs and Chinese herbal drugs);

Past medical history and surgical history:

• Past medical history includes structural heart diseases, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmias, Torsade de pointes, ventricular tachycardia, Long QT syndrome or signs and symptoms of Long QT syndrome with family history (evidenced by genetic testing or relatives died of sudden cardiac death at a young age);
• Thyroid disease history or received thyroid surgery;
• Immune diseases history (e.g. thymus disorder history);
• Received surgery within 6 months prior to the trial;
• Serious gastrointestinal disease history (e.g. clinically significant gallbladder disease, known or suspected jaundice, hepatocellular adenoma, hepatic cavernous hemangioma or other hepatic disease);
• Any gastrointestinal, hepatic or renal diseases that affect drug absorption or metabolism within 6 months prior to the trial (excluded regardless resolved);
• Any serious cerebrovascular, respiratory, metabolic and neurological disease history;
• Hematological disease like clotting disorder;
• Tumor history;
• Hypokalemia, hypocalcemia according to the lower limit of reference range provided by the clinical laboratory;

Lifestyle:

• Frequent alcohol intake within 6 months prior to the trial. Over 14 units of alcohol intake per week (1 unit = 17.7ml ethanol, 1 unit = 357 ml 5% alcohol beer or 44ml 40% liquor or 147 ml 12% alcohol wine);
• Smoke >1 cigarette per day within 3 months prior to the trial;
• Drug abuse history and taken drugs (marijuana, cocaine, opiates, benzodiazepines, amphetamines, barbiturates, methadone, tricyclic antidepressants, etc.) within 1 year prior to the trial;
• Drink excess tea, coffee or caffeine-containing drinks (more than 8 cups) per day 2 days before drug administration to 8 days after drug administration;
• Drink grapefruit juice 2 days before drug administration to 8 days after drug administration;

Others:

• Did not consent to use effective contraceptive methods from enrollment to 3 months after drug administration;
• Hypersensitivity including known allergy to the excipients of the drug (microcrystalline cellulose, lactose, silica powder, sodium carboxymethyl starch, magnesium stearate);
• Participated in any other clinical trials within 3 months prior to the trial or planned to participate in any other clinical trials 1 month after enrollment to the last drug administration visit;
• Blood donation within 3 months prior to the trial or planned to donate blood 1 month after enrollment to the last drug administration visit;
• Any food allergy or special request to diet and cannot comply to unified diet;
• Subjects considered to be excluded by investigator;

For female subjects, any following criteria met, apart from criteria above, should also be excluded:

• Taken oral contraceptive pills within 1 month prior to the trial;
• Long term use of estrogen or progesterone injection or implants within 6 months prior to the trial;
• Fertile female subjects without using contraceptive method 2 weeks prior to the trial;
• Fertile female subjects and spouse not consent to use following contraceptive method, condoms, intra-uterine device, etc. after enrollment to 3 months after drug administration;
• During pregnancy or lactation;
• Urine pregnancy test positive;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm	Drug: Propionyl-L-Carnitine Hydrochloride; 1g twice a day on first 4 days and 1g/ day on day 5 during Phase III

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve (AUC)	To observe area under curve characteristics of Propionyl-L-Carnitine in single or multiple dose groups	Day 3 and 4, 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24h after drug administration on day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cumulative urine excretion rate	To compare the cumulative urine excretion rate in multiple dose with that in single dose	0h-2h, 2-4h, 4-8h, 8-12h, 12-24h after drug administration

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited
• Investigators: Principal Investigator: Heng-yan Qu, National Clinical Trial Institution of Affiliated Hospital of Military Medical Sciences

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: May 24, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 30, 2016

Study Record Updates

• Last Update Posted (Estimate): May 30, 2016
• Last Update Submitted That Met QC Criteria: May 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: Zhaoke-201506-PLC-multidose