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. 2020 Jun 19;2020(6):CD012735. doi: 10.1002/14651858.CD012735.pub2

NK‐104.202 2013.

Study characteristics
Methods Study design: Randomised controlled trial
Study grouping: Parallel group
Method: 4‐week single‐blind placebo run‐in period; 12‐week randomised double‐blind placebo‐controlled study with evening dosing
Participants Baseline Characteristics
1 mg

  • n: 52

  • Total cholesterol: 7.3 mmol/L (282 mg/dL)

  • LDL cholesterol: 5.1 mmol/L (197 mg/dL)

  • HDL cholesterol: 1.4 mmol/L (54 mg/dL)

  • Triglycerides: 1.8 mmol/L (159 mg/dL)


2 mg

  • n: 49

  • Total cholesterol: 7.4 mmol/L (286 mg/dL)

  • LDL cholesterol: 5.2 mmol/L (201 mg/dL)

  • HDL cholesterol: 1.5 mmol/L (58 mg/dL)

  • Triglycerides: 1.8 mmol/L (159 mg/dL)


4 mg

  • n: 50

  • Total cholesterol: 7.4 mmol/L (286 mg/dL)

  • LDL cholesterol: 5.1 mmol/L (197 mg/dL)

  • HDL cholesterol: 1.4 mmol/L (54 mg/dL)

  • Triglycerides: 1.8 mmol/L (159 mg/dL)


8 mg

  • n: 49

  • Total cholesterol: 7.4 mmol/L (286 mg/dL)

  • LDL cholesterol: 5.1 mmol/L (197 mg/dL)

  • HDL cholesterol: 1.6 mmol/L (62 mg/dL)

  • Triglycerides: 1.6 mmol/L (142 mg/dL)


Placebo

  • n: 51

  • Total cholesterol: 7.4 mmol/L (286 mg/dL)

  • LDL cholesterol: 5.1 mmol/L (197 mg/dL)

  • HDL cholesterol: 1.5 mmol/L (58 mg/dL)

  • Triglycerides: 1.6 mmol/L (142 mg/dL)


Overall

  • n: 251


Included criteria: 18‐75 years; females of childbearing potential to be on oral contraception of at least 3 months; and willingness to adhere to the National Cholesterol Education Program (NCEP) Step‐1 or equivalent diet. Subjects had primary hypercholesterolaemia with LDL‐cholesterol ≥ 160 mg/dL (4.13 mmol/L) but ≤ 250 mg/dL (6.46 mmol/L), and triglyceride (TG) level ≤ 300 mg/dL (3.43 mmol/L) at Visit 3.
Excluded criteria: pregnancy, or not taking oral contraception; • BMI > 30 kg/m2; • alcohol abuse; • hypersensitivity to HMG‐CoA reductase inhibitors; • use of prohibited concomitant medications; • compliance 80% during run‐in period; • diabetes or fasting serum glucose ≥ 7 mmol/L at Visit 2; • renal impairment or serum creatinine > 1.8 mg/dL or nephrotic syndrome; • uncontrolled hypertension or diastolic blood pressure (DBP) ≥ 110 mmHg or systolic blood pressure (SBP) ≥ 180 mmHg; • history of myocardial infarction, unstable angina, stroke, transient ischaemic attack (TIA), percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG); • NYHA class 3 or 4 congestive cardiac failure; • active liver disease or AST or alanine aminotransferase (ALT) > 2 times ULN; • muscular or neuromuscular disease or creatinine kinase (CK) > 3 times ULN without explanation; • malignancy within past 10 years; • known cataracts; • human immunodeficiency virus (HIV) infection; • severe depression or suicidal tendencies; • Type I, IIb, III, IV or V hyperlipidaemia; • familial hypercholesterolaemia or LDL‐C > 250 mg/dL at Visit 3; and • hypercholesterolaemia secondary to hypothyroidism
Baseline Group Characteristics:NR
Interventions Intervention Characteristics
1 mg
2 mg
4 mg
8 mg
Placebo
Outcomes Total cholesterol

  • Outcome type: Continuous

  • Unit of measure: Percentage change from baseline

  • Direction: Lower is better


LDL cholesterol

  • Outcome type: Continuous

  • Unit of measure: Percentage change from baseline

  • Direction: Lower is better


HDL cholesterol

  • Outcome type: Continuous

  • Unit of measure: Percentage change from baseline

  • Direction: Higher is better


Triglycerides

  • Outcome type: Continuous

  • Unit of measure: Percentage change from baseline

  • Direction: Lower is better
Notes Stephen P on 22/11/2018 13:02
Included
8 mg dose: we used the adjusted mean and imputed SDs of the percentage change but adjusted means were not calculated for total cholesterol.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Judgement Comment: Method of sequence generation was not reported.
Allocation concealment (selection bias) Low risk Judgement Comment: A centralised randomising system was used.
Blinding of participants and personnel (performance bias)
All outcomes Low risk Judgement Comment: Double‐blind. Study medication was blinded and investigators did not receive lipid values during treatment period until after study completion.
Blinding of outcome assessment (detection bias)
All outcomes Low risk Judgement Comment: Lipid parameters were measured in a remote laboratory.
Selective reporting (reporting bias) Low risk Judgement Comment: LDL cholesterol outcome was reported.
Other bias High risk Judgement Comment: Trial sponsored by laboratories Negma, a pharmaceutical company in France.
Incomplete outcome data (attrition bias) Total cholesterol Low risk [(252 ‐ 249)/252]*100 = 1.2 % participants were not included in the efficacy analysis.
Incomplete outcome data (attrition bias) LDL cholesterol) Low risk [(252 ‐ 249)/252]*100 = 1.2 % participants were not included in the efficacy analysis.
Incomplete outcome data (attrition bias) HDL cholesterol Low risk [(252 ‐ 249)/252]*100 = 1.2 % participants were not included in the efficacy analysis.
Incomplete outcome data (attrition bias) Triglycerides Low risk [(252 ‐ 249)/252]*100 = 1.2 % participants were not included in the efficacy analysis.
Blinding of outcome assessment (detection bias)WDAEs High risk No WDAEs were reported.
Selective reporting (reporting bias) for WDAEs High risk No WDAE outcome reported