Hyperlipidemias
Conditions
Brief summary
Identified the efficacy of Antroquinonol (Hocena 50mg) in triglyceride, lipid-lowering and fatty liver.
Detailed description
The primary efficacy objective is to demonstrate the reduction of triglyceride (TG) by Antroquinonol, in comparison with placebo, after 12 weeks of treatment in patients with hypercholesterolemia and hyperlipidemia. Secondary objectives include the evaluation of the effects of Antroquinonol in comparison with placebo on other lipid parameters after 12 weeks of treatment and the effects of Antroquinonol on left ventricular diastolic function, arterial stiffness and fatty liver. The safety and tolerability of Antroquinonol will be monitored as well.
Interventions
DRUGAntroquinonol
Antroquinonol will be provided as capsules of 50 mg
DRUGplacebo
The matching placebo will be packaged as Antroquinonol with appearance identical in all aspects, however, don't have the active compound(antroquinonol)
Sponsors
Golden Biotechnology Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Adults of either sex 30 to 75 years of age, inclusive, with a diagnosis of nonfamilial hypercholesterolemia or mixed hyperlipidemia as one of the following: * TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL * TG between 150 mg/dL and 500 mg/dL and LDL-C \> 130 mg/dL); 2. Subject must be free of any clinically significant disease, other than nonfamilial hypercholesterolemia or mixed hyperlipidemia that would knowingly interfere with study evaluations; 3. A wash-out period of 2 weeks will be applied to patients prior treated with lipid-lowering medication; 4. Subject must be willing to adhere to protocol requirements, and provide written informed consent; 5. Female of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
Exclusion criteria
1. Patients with secondary dyslipidemia caused by diabetes mellitus, hypothyroidism, obstructive liver disease, chronic renal failure or drugs which can increase LDL-C level (e.g. retinoids, cyclosporine A and phenothiazines) or decrease HDL-C level (e.g. progestins, androgens, β-blockers, probucol and anabolic steroid) 2. Patients with lifestyle that may interfere treatment efficacy, such as alcoholism or drinking habits more than 3 times per week, late dinner, late night supper, frequent oversea business traveler, frequent social gathering, and patients who cannot anticipate a diet control and lifestyle changes; 3. Patients with diabetes or history of coronary artery disease (has had myocardial infarction, cardiac intervention, cerebrovascular accident/stroke or transient ischemic attack less than 6 months prior to Visit 1); 4. Patients with hypertension that is uncontrolled defined as 2 consecutive measurements of sitting blood pressure of systolic \>140 mmHg or diastolic \> 90 mmHg at Visit 1; 5. Patient has a known hypersensitivity to Antroquinonol or related compounds; 6. Patient with uncontrolled intercurrent illness including, but not limited to, acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require IV therapy), right heart failure due to severe pulmonary disease, diagnosed peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 1, or psychiatric illness/social situations that would limit compliance with study requirements; 7. Patients with a history of heart transplant or who are on a transplant list or with left ventricular assistance device (LVAD device); 8. Patients with documented ventricular arrhythmia with syncopal episodes within the past 3 months prior to visit 1 that remained untreated; 9. Patients with confirmed severe primary pulmonary, renal (eGFR\<30 ml/min/1.73 m2) or hepatic (Child-Pugh B/C classification) disease; 10. Patients who can't stop current lipid lowering drug treatments based on investigator's judgement; 11. Patients with any malignancy, treated or untreated, within the past 5 years of Visit 1 whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin or carcinoma in situ of the cervix; 12. Female patient during pregnancy, lactation or breastfeeding; 13. Patient has any other life-threatening complications; 14. Patient who is considered unreliable as to medication compliance or adherence to scheduled appointments, or inappropriate for inclusion determined by the investigators; 15. Any other reasons addressed by the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TG Change (mg/dL ) | 12 weeks | value at 12 weeks minus value at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LDL& HDL (mg/dL) | 12 weeks | value at 12 weeks minus value at baseline of PP pupulation in HDL/LDL ratio. |
| Non-invasive Arterial Stiffness Measurement | 12 weeks | To evaluate the effect of Antroquinonol via a non-invasive arterial stiffness measurement. |
| Fatty Liver | 12 weeks | To evaluate the recover fatty liver effect of Antroquinonol on patients who with fatty liver by Investigator |
Countries
Taiwan
Participant flow
Recruitment details
A multi-center, phase II, prospective, double blind, randomized, placebo-controlled trial, recruiting from 23-Jun-2016 to 30-Aug-2018 6 sites are NTUniversity Hospital; CMU Hospital; NCKU Hospital; Taipei VG Hospital; FEM Hospital; CGM Hospital, Linkou branch;
Pre-assignment details
total treatment period: 16 weeks including a 2-week screening visit, a 12-week study treatment, and a 2-week follow-up
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (Placebo) 3 capsules once a day.
placebo: The matching placebo will be packaged as Antroquinonol with appearance identical in all aspects, however, don't have the active compound(antroquinonol) | 30 |
| Antroquinonol 50 mg PO Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (1 capsule of antroquinnonol 50mg and 2 capsules of Placebo) 3 capsules once a day.
Antroquinonol: Antroquinonol will be provided as capsules of 50 mg | 30 |
| Antroquinonol 100 mg PO Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (2 capsules of antroquinnonol 50mg and 1 capsule of Placebo) 3 capsules once a day.
Antroquinonol: Antroquinonol will be provided as capsules of 50 mg | 30 |
| Antroquinonol 150 mg PO Subjects with screening central laboratory with a diagnosis of primary hypercholesterolemia (nonfamilial) or mixed hyperlipidemia (TG between 150 mg/dL and 500 mg/dL, and cholesterol between 160 mg/dL and 250 mg/dL or LDL-C \> 130 mg/dL ) who meet inclusion/exclusion criteria will be randomized to 4 groups patient will take (antroquinnonol 50mg ) 3 capsules once a day.
Antroquinonol: Antroquinonol will be provided as capsules of 50 mg | 30 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 4 | 8 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Use of prohibited medication | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Antroquinonol 100 mg PO | Antroquinonol 50 mg PO | Antroquinonol 150 mg PO | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 15.12 | 48.9 years STANDARD_DEVIATION 10.32 | 53.3 years STANDARD_DEVIATION 13.18 | 52.5 years STANDARD_DEVIATION 9.98 | 50.70 years STANDARD_DEVIATION 12.37 |
| BMI | 28.4 kg/m^2 STANDARD_DEVIATION 4.71 | 28.4 kg/m^2 STANDARD_DEVIATION 5.41 | 27.2 kg/m^2 STANDARD_DEVIATION 3.8 | 26.8 kg/m^2 STANDARD_DEVIATION 3.72 | 27.68 kg/m^2 STANDARD_DEVIATION 4.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 30 Participants | 30 Participants | 30 Participants | 120 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 30 participants | 30 participants | 30 participants | 30 participants | 120 participants |
| Sex: Female, Male Female | 12 Participants | 5 Participants | 10 Participants | 8 Participants | 35 Participants |
| Sex: Female, Male Male | 18 Participants | 25 Participants | 20 Participants | 22 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 14 | 8 / 13 | 12 / 19 | 17 / 18 |
| other Total, other adverse events | 8 / 14 | 8 / 13 | 12 / 19 | 17 / 18 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 | 1 / 19 | 0 / 18 |
Outcome results
Primary
TG Change (mg/dL )
value at 12 weeks minus value at baseline
Time frame: 12 weeks
Population: Per-protocol population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | TG Change (mg/dL ) | -9.2 percentage of change |
| Antroquinonol 50 mg PO | TG Change (mg/dL ) | 14.6 percentage of change |
| Antroquinonol 100 mg PO | TG Change (mg/dL ) | -4.2 percentage of change |
| Antroquinonol 150 mg PO | TG Change (mg/dL ) | -1.3 percentage of change |
Secondary
Fatty Liver
To evaluate the recover fatty liver effect of Antroquinonol on patients who with fatty liver by Investigator
Time frame: 12 weeks
Population: Only Per-protocol population subjects with abnormal liver attenuation at baseline subjected to follow-up after 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Fatty Liver | 0 Participants |
| Antroquinonol 50 mg PO | Fatty Liver | 4 Participants |
| Antroquinonol 100 mg PO | Fatty Liver | 1 Participants |
| Antroquinonol 150 mg PO | Fatty Liver | 1 Participants |
Secondary
LDL& HDL (mg/dL)
value at 12 weeks minus value at baseline of PP pupulation in HDL/LDL ratio.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LDL& HDL (mg/dL) | 2.4 percentage of change | Standard Deviation 21.73 |
| Antroquinonol 50 mg PO | LDL& HDL (mg/dL) | 5.1 percentage of change | Standard Deviation 23.02 |
| Antroquinonol 100 mg PO | LDL& HDL (mg/dL) | -1.1 percentage of change | Standard Deviation 15.51 |
| Antroquinonol 150 mg PO | LDL& HDL (mg/dL) | 0.3 percentage of change | Standard Deviation 13.98 |
Secondary
Non-invasive Arterial Stiffness Measurement
To evaluate the effect of Antroquinonol via a non-invasive arterial stiffness measurement.
Time frame: 12 weeks
Population: Per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Non-invasive Arterial Stiffness Measurement | 3.1 percentage of change | Standard Deviation 9.58 |
| Antroquinonol 50 mg PO | Non-invasive Arterial Stiffness Measurement | 0.0 percentage of change | Standard Deviation 13.8 |
| Antroquinonol 100 mg PO | Non-invasive Arterial Stiffness Measurement | -3.3 percentage of change | Standard Deviation 10.38 |
| Antroquinonol 150 mg PO | Non-invasive Arterial Stiffness Measurement | 2.8 percentage of change | Standard Deviation 9.84 |