CompletedPhase 1ACTRN12618001929291

A human trial to evaluate the performance and safety of a new formulation containing a cholesterol-lowering drug to healthy male volunteers.

A Phase I, Proof-of-Concept, Randomised, Double-Blind, Cross-Over Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetic Profile of LipoCeramic™ Simvastatin.

Sponsor

Reform Pharm Pty Ltd

Enrollment

14 participants

Start Date

Mar 8, 2019

Study Type

Interventional

Conditions

Hypercholesterolemia

Summary

The purpose of this study is to evaluate the safety and performance of LipoCeramic simvastatin when administered as an oral capsule. Simvastatin is a commonly prescribed lipid-regulating drug which is used to treat hypercholesterolemia, where there is high levels of cholesterol present in the blood. LipoCeramic technology combines simvastatin with numerous approved ingredients to improve the absorption of the drug in the body. A total of twelve healthy male volunteers aged 18 or over, who meet all entry criteria will be accepted into the study. Participants will be randomly allocated to two groups which dictates which formulation they receive. The trial will be “double- blinded” which means neither the participants, nor the study staff, will know which formulations are being administered. Volunteers will undergo a screening process to determine their eligibility for the study. Successfully recruited volunteers will be required to attend the Clinical Trial Facility on three occasions for a full-day (8:00 am to 5:30 pm) visit, where they will receive one oral dose of a commercial simvastatin tablet and two doses of simvastatin in a LipoCeramic Formulation. There will be a 7-day wash-out period between doses, meaning volunteers will return to the Clinical Trial Facility 7 days and 14 days after administration of their first dose to receive subsequent treatments. Each dosing day will require blood sample collection prior to dosing and at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours post dose administration. Numerous safety assessments will also be performed throughout the day. The study will be held at the University of South Australia Clinical Trial Facility, located at the City East Campus, Bonython Jubilee Building, Frome Road. Volunteers will be financially reimbursed $600 for their time and inconvenience after completion of the study.

Eligibility

Sex: MalesMin Age: 18 Yearss

Inclusion Criteria6

Gender: Male.
Age: 18 years and over.
General Health: Healthy. Health status will be determined by the subject’s medical history with specific attention to: (I) drug history identifying any known drug allergies or drug abuse, (II) any chronic use of medication, and (III) a thorough review of body systems. This will also be determined after a physical examination, including an electrocardiogram (ECG), revealing no abnormal findings, which in the opinion of the Principal Investigator, or medical nominee, would risk the safety of the subject of impact the validity of the study results.
Venous Access: Subjects require adequate venous access on their left or right arm to allow for collection of numerous blood samples.
Language: Fluent in English.
Informed Consent: Subject must voluntarily give written informed consent to participate in this study.

Exclusion Criteria15

Hypersensitivity: History of hypersensitivity and/or allergy to simvastatin or any of the ingredients which are listed in the formulation, including soy. Hypersensitivity to lignocaine/lidocaine or any surgical dressings which may be used during the study.
Medical Conditions: (a) History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders. (b) Any pre-existing condition which may interfere with the absorption, distribution, metabolism and/or excretion of drugs. (c) History of abnormal bleeding tendencies or thrombophlebitis unrelated to venous puncture or intravenous cannulation, or a history of Hepatitis B or C, or a positive test for Hepatitis antigen or antibodies, a history of HIV infection or presence of HIV antibodies.
Abnormal Laboratory Results: Any evidence of organ dysfunction or abnormality in clinical laboratory results which is deemed significant which would risk the safety of the subject of impact the validity of the study results.
Ethanol Use: Regular drinkers who consume more than four units of alcohol daily or those who may have difficulty abstaining from alcohol for 24 hours prior to dose administration and 8.5 hours following dose administration.
Drug and Alcohol Abuse: History or current evidence of alcohol or drug abuse, licit or illicit, or positive urine drug and breath alcohol screen.
Medication: Difficulty in refraining from the administration of potent CYP3A4 inhibitors for 14 days prior to the initial dose administration and until the exit evaluation. Subjects will be instructed not to take any prescription medication for 14 days prior to the first dose administration and for the duration of the study and to abstain from over- the-counter (OTC) medication within 7 days prior to initial dose administration and until the Exit Evaluation.
Xanthine Use: Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines (I.e. coffee, tea, cola and chocolate) during 24 hours prior to dose administration until the completion of blood sampling in each study period.
Psychiatric or Psychological Disorder: History or presence of any psychiatric ill ness or psychological disorder which may impair the subject’s ability to provide written consent or participate in the study.
Blood Donation: Standard blood donation (usually 550 mL) within the 12-week period before dose administration until the exit evaluation.
Dietary Habits: Unusual dietary habits including vegetarian diets, excessive or unusual vitamin intake. Difficulty in abstaining from grapefruit juice for 24 hours prior to dose administration until the exit evaluation.
Food Consumption: Difficulty in refraining from food consumption from 2300 hours the night before dosing (I.e. for 10 hours prior to dosing).
Tobacco: Tobacco users who smoke more than 10 cigarettes (or equivalent) per day and/or who are unable to refrain from smoking whilst confined in the Clinical Trial Facility each study period.
Contraception: Unwilling to use adequate contraception for the duration of the study (e.g. condoms), unless surgically sterile
Recent Study Participation: Consumption of any drug as part of a research study within 30 days of the initial dose administration in this study.
Protocol Compliance: Poor compliers or those who are unlikely to attend.

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Interventions

Simvastatin will be delivered in a new LipoCeramic formulation which contains soybean lecithin, Capmul MCM and silica nanoparticles. Two variations of silica nanoparticles will be trialled including Aerosil 300 and Syloid 224. These formulations will be referred to as LipoCeramic Formulation A and LipoCeramic Formulation B, respectively. Volunteers will also be randomly assigned into Treatment Group 1 or Treatment Group 2 where they will be orally administered a simvastatin dose of 10 mg and 20 mg in LipoCeramic Formulation A or LipoCeramic Formulation B, respectively. Each dose will be administered with 240 mL of room temperature water following overnight fasting (at least 10 hours). Between each dose, there will be a 7 day wash-out period. Prior to each dosing day, a reminder of the need to fast will be sent to the participant. During check-in on each dosing day, the participants will undergo a brief questionnaire to ensure they still adhere to the inclusion criteria and have not violated any exclusion criteria, including food intake. All doses will be administered by a nurse and the oral cavity will be checked to ensure the capsule has been swallowed.