Hypercholesterolemia
Conditions
Keywords
HMG-CoA reductase inhibitors
Brief summary
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.
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.
Interventions
DRUG1PC002
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.
DRUGLipitor
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.
Sponsors
Orient Europharma Co., Ltd.
Orient Pharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Change From Baseline in LDL-C Level at Week 12. | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LDL-C | week 4 | Percent change from baseline in LDL-C level at Week 4 |
| HDL-C | week 4 | Percent change from baseline in HDL-C level at Week 4 |
| Triglyceride | week 4 | Percent change from baseline in TG level at Week 4 |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1PC002 2 mg 1PC002 once daily for 12 weeks.
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. | 103 |
| Lipitor 10 mg atorvastatin once daily for 12 weeks.
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. | 99 |
| Total | 202 |
Baseline characteristics
| Characteristic | 1PC002 | Lipitor | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 6 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants | 93 Participants | 180 Participants |
| Age, Continuous | 55.36 years STANDARD_DEVIATION 10.5 | 57.90 years STANDARD_DEVIATION 8.8 | 56.60 years STANDARD_DEVIATION 9.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 99 Participants | 202 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 103. participants | 99 participants | 202 participants |
| Sex: Female, Male Female | 60 Participants | 57 Participants | 117 Participants |
| Sex: Female, Male Male | 43 Participants | 42 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 103 | 55 / 99 |
| serious Total, serious adverse events | 3 / 103 | 1 / 99 |
Outcome results
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipitor | The Percentage Change From Baseline in LDL-C Level at Week 12. | -42.89 Percent change from baseline | Standard Deviation 12.8 |
| 1PC002 | The Percentage Change From Baseline in LDL-C Level at Week 12. | -37.43 Percent change from baseline | Standard Deviation 17.97 |
Secondary
HDL-C
Percent change from baseline in HDL-C level at Week 4
Time frame: week 4
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipitor | HDL-C | 0.06 Percent change from baseline | Standard Deviation 10.49 |
| 1PC002 | HDL-C | -1.64 Percent change from baseline | Standard Deviation 11.01 |
Secondary
LDL-C
Percent change from baseline in LDL-C level at Week 4
Time frame: week 4
Population: ITT population had been analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipitor | LDL-C | -39.01 Percent change from baseline | Standard Deviation 13.04 |
| 1PC002 | LDL-C | -40.07 Percent change from baseline | Standard Deviation 12.18 |
Secondary
Triglyceride
Percent change from baseline in TG level at Week 4
Time frame: week 4
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipitor | Triglyceride | -18.75 Percent change from baseline | Standard Deviation 26.9 |
| 1PC002 | Triglyceride | -19.5 Percent change from baseline | Standard Deviation 25.5 |