Efficacy and Safety Study of Pitavastatin for Hypercholesterolemia

A Prospective, Double-blind, Randomized, Parallel, Multiple-center Study to Compare the Efficacy and Safety of 1PC002 and Atorvastatin in Taiwanese Patients With Hypercholesterolemia

1PC002 is a newly developed synthetic and highly potent HMG-CoA reductase inhibitor. Its active compound, pitavastatin has recently been approved by US FDA for indications of primary hypercholesterolemia and combined dyslipidaemia. It exhibits unique pharmacokinetic properties. Unlike atorvastatin which is metabolized by CYP3A4, metabolism of 1PC002 does not depend on CYP3A4. This multi-center study is conducted to confirm the efficacy and safety of 1PC002 administered for 12 weeks is non-inferior to atorvastatin.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: 1PC002; Drug: Lipitor

Detailed Description

This is a prospective, active-controlled, double-blind, randomized, parallel, and multi-center study. To target 150 evaluable subjects, approximately 200 Taiwanese patients with primary hypercholesterolemia or combined dyslipidemia will be enrolled in this study.

After providing the written inform consent, patients will undergo a complete physical examination, vital sign (brachial BP / HR), medical history, and lab assessment, including fasting serum LDL-C, TC, HDL-C, TG, and non-HDL. They should not take any hypolipidemic drugs for at least 4 weeks prior to initiation of study treatment. All eligible subjects will be randomized into 2 groups in a 1:1 ratio to receive either 2 mg 1PC002 or 10 mg atorvastatin once daily for 12 weeks.

• Study Group: 1PC002 1 cap. q.d. p.o.
• Control Group: Atorvastatin 1 cap. q.d. p.o.

After entering the baseline visit, lipid profiles (including fasting serum LDL-C, TC, HDL-C, TG, non-HDL, Apo A1, Apo B and Apo B / Apo A1 ratio), hs-CRP, eGFR, spot urinary albumin / creatinine ratio (ACR) and central BP values will be obtained at baseline, Week 4 and Week 12 for evaluating the effectiveness of study drugs and for any possible changes in laboratory data. Non-HDL value will be calculated by subtracting HDL-C from TC. Moreover, serum Cystatin C, another biomarker of renal function, will also be assessed at baseline and Week 12.

For monitoring the safety, biochemical and hematological assessment will be performed at baseline, Week 4 and 12. Additional liver function and CK test will be conducted at Week 8. The occurring AE(s) and SAE will be followed until resolution or the event is considered stable.

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University - Shuang Ho Hospital
  • New Taipei City, Taiwan, 231
    • Cardinal Tien Hospital
  • New Taipei City, Taiwan, 23142
    • Buddhist Taipei TzuChi General Hospital
  • Taichung City, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei City, Taiwan, 114
    • Tri-Service General Hospital
  • Taipei City, Taiwan, 112
    • Cheng Hsin General Hospital
  • Taoyuan City, Taiwan, 333
    • Chang Gung Medical Foundation- LinKuo Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Females or males aged between 20 and 80 years.

2. Subjects who meet All of the following diagnosis at screening visit:

   • Primary hypercholesterolemia or combined dyslipidemia
   • TC ≥ 220 mg/dL or LDL-C ≥ 130 mg/dL
   • TG < 400 mg/dL
3. Subjects who is willing and able to provide ICF.

Exclusion Criteria:

1. Females who are pregnant, breast-feeding or intent to be pregnant during study period, or those of childbearing potential not using effective contraception.
2. Subject with documented homozygous familial hypercholesterolemia.
3. Subject with documented HIV.
4. Subject with documented hypothyroidism and inadequate treatment judged by investigator.
5. Subjects with unstable cardiovascular disease (CVD) prior to randomization.
6. Subjects with hepatic or biliary disorders, such as acute hepatitis, acute exacerbation of chronic hepatitis, liver cirrhosis, liver cancer and jaundice.
7. Any condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.

8. Subjects with the following lab data at screening visit:

   • serum creatine kinase (CK) > 5 x upper limit of normal (ULN)
   • ALT or AST of > 3 x ULN
   • serum creatinine ≥ 1.5 mg/dL
   • HbA1c > 8.0%

9. Subject with the following past histories:

   • hypersensitivity to statins or any other ingredients of study drugs
   • resistant to statins treatment
10. Use of any lipid-lowering agents within 4 weeks prior to the initiation of study treatment.
11. Use of any investigational product within 4 weeks prior to screening.
12. Any unstable concomitant disease or clinical condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk to participate in the study or confounds the ability to interpret data from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1PC002; 2 mg 1PC002 once daily for 12 weeks.	Drug: 1PC002; Subjects should be instructed to take 1 capsule of study drug (1PC002 or atorvastatin) orally once a day, with or without food. Administration before bedtime or at regular time-interval is recommended.; Other Names: Pitavastatin
Active Comparator: Lipitor; 10 mg atorvastatin once daily for 12 weeks.	Drug: Lipitor; Subjects should be instructed to take 1 capsule of study drug (1PC002 or atorvastatin) orally once a day, with or without food. Administration before bedtime or at regular time-interval is recommended.; Other Names: Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage Change From Baseline in LDL-C Level at Week 12.	The study aimed to test that the efficacy of 1PC002 group was non-inferior to Atorvastatin group in percent change from baseline of LDL-C level at Week 12.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-C	Percent change from baseline in LDL-C level at Week 4	week 4
HDL-C	Percent change from baseline in HDL-C level at Week 4	week 4
Triglyceride	Percent change from baseline in TG level at Week 4	week 4

Collaborators and Investigators

• Sponsor: Orient Pharma Co., Ltd.
• Collaborators: Orient Europharma Co., Ltd.
• Investigators: Principal Investigator: Chiau-Suong Liau, Buddhist Taipei TzuChi General Hospital; Principal Investigator: Ming-Shien Wen, Chang Gung Medical Foundation- LinKuo Branch; Principal Investigator: Wen-Pin Huang, Cheng-Hsin general hospital; Principal Investigator: Dee Pei, Cardinal Tien Hospital; Principal Investigator: Wei-Shiang Lin, Tri-Service General Hospital; Principal Investigator: Huey-Herng Sheu, Taichung Veterans General Hospital; Principal Investigator: Chen-Huan Chen, Taipei Veterans General Hospital, Taiwan; Principal Investigator: Ju-Chi Liu, Taipei Medical University Shuang Ho Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimated): October 18, 2012

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: August 26, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: HMG-CoA reductase inhibitors
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Pitavastatin
• Other Study ID Numbers: QCR10022