Clinical Trial Results:
The Efficacy and Safety of ROSUvastatin Dose Titration in the Treatment of PATients with Hyperlipidemia (ROSU-PATH)
Summary
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EudraCT number |
2012-004799-21 |
Trial protocol |
SI CZ HU |
Global end of trial date |
31 Jul 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Jun 2020
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First version publication date |
24 Jun 2020
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Other versions |
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Summary report(s) |
ROSU-PATH Final Report Synopsis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
KCT03/2012
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Krka, d.d., Novo mesto
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Sponsor organisation address |
Dunajska cesta 65, Ljubljana, Slovenia, 1000
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Public contact |
Tanja Kohek, Krka, d.d., Novo mesto
Dunajska cesta 65
1000 Ljubljana, 00386 1 4751236, tanja.kohek@krka.biz
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Scientific contact |
Tanja Kohek, Krka, d.d., Novo mesto
Dunajska cesta 65
1000 Ljubljana, 00386 1 4751236, tanja.kohek@krka.biz
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Sponsor organisation name |
Krka ČR, s.r.o.
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Sponsor organisation address |
Sokolovská 192/79, Prague, Czech Republic, 180 00
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Public contact |
Martin Sustr, Krka ČR, s.r.o.
Sokolovská 192/79
180 00 Prague, 00420 602 486846, martin.sustr@krka.biz
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Scientific contact |
Martin Sustr, Krka ČR, s.r.o.
Sokolovská 192/79
180 00 Prague, 00420 602 486846, martin.sustr@krka.biz
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Sponsor organisation name |
KRKA Magyarország Kereskedelmi Kft.
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Sponsor organisation address |
Dunavirág u. 2-6. 3.torony, 3.em., Budapest, Hungary, 1138
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Public contact |
Ágota Mészáros, KRKA Magyarország Kereskedelmi Kft.
Dunavirág u. 2-6. 3.torony, 3.em.
1138 Budapest
Hungary, +362 0 8012549, agota.meszaros@krka.biz
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Scientific contact |
Ágota Mészáros, KRKA Magyarország Kereskedelmi Kft.
Dunavirág u. 2-6. 3.torony, 3.em.
1138 Budapest
Hungary, +362 0 8012549, agota.meszaros@krka.biz
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Sponsor organisation name |
KRKA-RUS LLC
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Sponsor organisation address |
Vodny Business Center, 22nd floor, 5/1 Golovinskoye Highway, Moscow, Russian Federation, 125212
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Public contact |
Anna Zakharova, KRKA-RUS LLC
Vodny Business Center, 22nd floor, 5/1 Golovinskoye Highway
125212 Moscow
Russia, anna.zakharova@krka.biz
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Scientific contact |
Anna Zakharova, KRKA-RUS LLC
Vodny Business Center, 22nd floor, 5/1 Golovinskoye Highway
125212 Moscow
Russia, anna.zakharova@krka.biz
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Sponsor organisation name |
KRKA Romania S.R.L.
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Sponsor organisation address |
Sema Parc, etaj 10, Sector 6, Bucharest, Romania, 060032
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Public contact |
Cristina Boeriu, KRKA Romania S.R.L.
Sema Parc, etaj 10, Sector 6
060032 Bucharest
Romania, 0040 72 9990907, cristina.boeriu@krka.biz
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Scientific contact |
Cristina Boeriu, KRKA Romania S.R.L.
Sema Parc, etaj 10, Sector 6
060032 Bucharest
Romania, 0040 72 9990907, cristina.boeriu@krka.biz
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Sponsor organisation name |
KRKA UKRAINE LLC
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Sponsor organisation address |
Ul. Staronavodnitskaya 13, of. 127, PB 42, Kiev, Ukraine, 01015
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Public contact |
Pavlo Radchuk, KRKA UKRAINE LLC
Ul. Staronavodnitskaya 13, of. 127, PB 42
01015 Kiev
Ukraine, pavlo.radchuk@krka.biz
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Scientific contact |
Pavlo Radchuk, KRKA UKRAINE LLC
Ul. Staronavodnitskaya 13, of. 127, PB 42
01015 Kiev
Ukraine, pavlo.radchuk@krka.biz
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Jan 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The aim of the study is to establish the efficacy and safety of Roswera® in wide populations of patients with primary hypercholesterolemia and mixed dyslipidemia (type IIb) (patients with high absolute risk for cardiovascular diseases in primary and secondary prevention) with emphasis on placement of additional strengths 15 mg and 30 mg in clinical practice.
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Protection of trial subjects |
The study was conducted in accordance with the ethical principles that are based on the Declaration of Helsinki.
In general patients aged 18-75 years of both genders with primary hypercholesterolemia or mixed dyslipidemia (type IIb) were eligible for the inclusion in the study. Prior to any study activities patients needed to sign written informed consent form. The dose of Rosuvastatin was adjusted on V2 (4 weeks) and on V3 (8 weeks) according to trial scheme and target lipid values.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Mar 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Croatia: 50
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Country: Number of subjects enrolled |
Ukraine: 52
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Country: Number of subjects enrolled |
Russian Federation: 122
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Country: Number of subjects enrolled |
Romania: 54
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Country: Number of subjects enrolled |
Slovenia: 67
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Country: Number of subjects enrolled |
Czech Republic: 65
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Country: Number of subjects enrolled |
Hungary: 62
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Worldwide total number of subjects |
472
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EEA total number of subjects |
298
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
367
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From 65 to 84 years |
105
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85 years and over |
0
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Recruitment
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Recruitment details |
There were 472 patients enrolled in the study. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
In general patients aged 18-75 years of both genders with primary hypercholesterolemia or mixed dyslipidemia (type IIb) were eligible for the inclusion in the study. Prior to any study activities patients needed to sign written informed consent form. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 10 | |||||||||||||||||||||||||||
Arm description |
All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Roswera® 10
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 10 contains 10 mg of rosuvastatin per tablet.
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Investigational medicinal product name |
Roswera® 20
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 20 contains 20 mg of rosuvastatin per tablet.
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Investigational medicinal product name |
Roswera® 40
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 40 contains 40 mg of rosuvastatin per tablet.
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Arm title
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Group 15 | |||||||||||||||||||||||||||
Arm description |
All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Roswera® 15
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 15 contains 15 mg of rosuvastatin per tablet.
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Investigational medicinal product name |
Roswera® 30
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 30 contains 30 mg of rosuvastatin per tablet.
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Investigational medicinal product name |
Roswera® 40
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 tablet per day at any time during the day, throughout the trial at the same time. Roswera® 40 contains 40 mg of rosuvastatin per tablet.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 10
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Reporting group description |
All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg. | ||
Reporting group title |
Group 15
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Reporting group description |
All patients meeting inclusion criteria were randomized at the start of the trial course (Visit 1) into two groups to receive either 10 mg/day or 15 mg/day of rosuvastatin. On V2 (after 4 weeks) and V3 (after 8 weeks) the dose was adjusted according to achievement of target LDL-c goals. If the patient did not achieve target LDL-c goal, the dose was increased according to the trial scheme. Patients starting the treatment with 10 mg/day of Roswera® were titrated according to the regimen 10 mg – 20 mg – 40 mg. Patients starting the treatment with 15 mg/day of Roswera® were titrated according to the regimen 15 mg – 30 mg – 40 mg. |
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End point title |
Efficacy of Roswera® in achieving target LDL-c levels | |||||||||||||||||||||
End point description |
The primary efficacy endpoint was to evaluate efficacy of Roswera® in achieving 2011 ESC/EAS guidelines target LDL-c levels in patients with hyperlipidemia. At each control visit, the serum lipids were measured and according to results, the achievement of target lipid levels was obtained.
During the trial, the proportion of patients achieving target LDL-c values was steadily increasing. At the end of the trial, 62% of patients in Group 10 and 73% of patients in Group 15 achieved target LDL-c levels.
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End point type |
Primary
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End point timeframe |
12 weeks for one patient and was the same for the whole duration of the study (FPI 14.3.2013 - LPO 31.7.2015).
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Statistical analysis title |
Difference between groups | |||||||||||||||||||||
Statistical analysis description |
Because of the reasonably large sample, the asymptotic z-test was employed to assess the difference between means of two variables measured in the same population. Asymptotic 95%-confidence interval for the difference between means was used for interval estimation.
The difference in proportion of patients achieving target LDL-c levels was statistically significant between Group 10 and Group 15 on each control visit (p < 0.0001 on V3 and V4; p < 0.05 on V2) and was in favour of Group 15.
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Comparison groups |
Group 10 v Group 15
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Number of subjects included in analysis |
462
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
< 0.05 | |||||||||||||||||||||
Method |
asymptotic z-test | |||||||||||||||||||||
Confidence interval |
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End point title |
LDL-c values across visits | ||||||||||||||||||||||||
End point description |
The primary efficacy endpoint was to evaluate efficacy of Roswera® in achieving 2011 ESC/EAS guidelines target LDL-c levels in patients with hyperlipidemia. At each control visit, the serum lipids were measured and according to results, the achievement of target lipid levels was obtained.
Group 10: The mean LDL-c values at the beginning and at the end of the trial were 4.33 ± 1.11 mmol/l and 2.36 ± 0.72 mmol/l, respectively. The mean LDL-c decreased statistically significantly from the V1 to V2 (p < 0.0001) and from V2 to V3 (p < 0.0001).
Group 15: The mean LDL-c values at the beginning and at the end of the trial were 4.44 ± 1.02 mmol/l and 2.28 ± 0.66 mmol/l, respectively. The mean LDL-c decreased statistically significantly from the V1 to V2 (p < 0.0001) and from V2 to V3 (p < 0.0001).
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End point type |
Primary
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End point timeframe |
12 weeks for one patient and was the same for the whole duration of the study ( FPI 14.3.2013 - LPO 31.7.2015).
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Statistical analysis title |
comparison between two visits | ||||||||||||||||||||||||
Statistical analysis description |
Because of the reasonably large sample, the asymptotic z-test was employed to assess the difference between means of two variables measured in the same population. Asymptotic 95%-confidence interval for the difference between means was used for interval estimation.
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Comparison groups |
Group 10 v Group 15
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Number of subjects included in analysis |
469
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||
Method |
Asymptotic z-test | ||||||||||||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
12 weeks for one patient and was the same for the whole duration of the study (FPI 14.3.2013 - LPO 31.7.2015).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
All patients
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Reporting group description |
All 472 patients that were included in the ITT analysis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |