Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin

Hypercholesterolemia Clinical Trial

— ODYSSEY-NIPPON  

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02584504
• Other study ID #: EFC14305
• Secondary ID: U1111-1170-7697
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2015
• Est. completion date: January 9, 2018

Study information

• Verified date: January 2019
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab administration as add-on therapy to non-statin lipid modifying therapy (LMT) including diet therapy alone or the lowest strength of statin in comparison with placebo after 12 weeks of treatment in participants with hypercholesterolemia.

Secondary Objective:

• To evaluate the effect of two treatment regimens of alirocumab on other lipid parameters: apolipoprotein B (Apo-B), non-high-density lipoprotein cholesterol (non HDL-C), total cholesterol (TC), lipoprotein (a) (Lp[a]), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoprotein A-1 (Apo A-1).

• To evaluate the safety and tolerability of alirocumab administration.

• To evaluate the development of anti-alirocumab antibodies.

• To evaluate the pharmacokinetic and pharmacodynamic profiles of alirocumab administration.

• To evaluate the long-term safety in participants receiving open-label alirocumab administration.

Description:

The duration of study per participant was approximately 71 weeks consisting of a run-in period (4 weeks), a screening period (3 weeks), a double-blind treatment period (12 weeks), and an open-label treatment period (52 weeks).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: January 9, 2018
• Est. primary completion date: April 5, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion criteria :

Participants with hypercholesterolemia (heFH or non-FH) receiving non statin LMTs or the lowest strength of statin.

Exclusion criteria:

• LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in participants with heFH or in participants with non-FH who have a history of documented coronary heart disease.

• LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit (Week -3) in participants with non-FH participants who had a history of documented diseases or other risk factors classified as primary prevention category III as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

• Not on a stable dose of LMT (including diet therapy alone) in the run-in period or the screening period.

• Fasting serum TGs >400 mg/dL (>4.52 mmol/L) at the screening period.

• Systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg at the run-in visit (Week -7) or the screening visit (Week -3) or the randomization visit (Week 0).

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
• Placebo
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
• Atorvastatin
Atorvastatin 5 mg tablet orally.
• Non-statin Lipid-Modifying Therapy
Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Other:
• Diet Alone
Stable cholesterol-lowering diet as background therapy.

Locations

Country	Name	City	State
Japan	Investigational Site Number 392028	Ageo-Shi
Japan	Investigational Site Number 392007	Chuo-Ku
Japan	Investigational Site Number 392029	Chuo-Ku
Japan	Investigational Site Number 392014	Fukui-Shi
Japan	Investigational Site Number 392023	Hachioji-Shi
Japan	Investigational Site Number 392013	Itoshima-Shi
Japan	Investigational Site Number 392010	Kanazawa-Shi
Japan	Investigational Site Number 392024	Kasuga-Shi
Japan	Investigational Site Number 392004	Kawanishi-Shi
Japan	Investigational Site Number 392015	Kitakyushu-Shi
Japan	Investigational Site Number 392005	Komatsu-Shi
Japan	Investigational Site Number 392032	Matsudo-Shi
Japan	Investigational Site Number 392017	Matsumoto-Shi
Japan	Investigational Site Number 392003	Mito-Shi
Japan	Investigational Site Number 392018	Morioka-Shi
Japan	Investigational Site Number 392009	Moriya-Shi
Japan	Investigational Site Number 392006	Nagoya-Shi
Japan	Investigational Site Number 392011	Nagoya-Shi
Japan	Investigational Site Number 392019	Nagoya-Shi
Japan	Investigational Site Number 392025	Nagoya-Shi
Japan	Investigational Site Number 392027	Osaka-Shi
Japan	Investigational Site Number 392030	Sakura-Shi
Japan	Investigational Site Number 392016	Shinagawa-Ku
Japan	Investigational Site Number 392001	Shinjuku-Ku
Japan	Investigational Site Number 392008	Shinjuku-Ku
Japan	Investigational Site Number 392012	Shizuoka-Shi
Japan	Investigational Site Number 392002	Suita-Shi
Japan	Investigational Site Number 392031	Suita-Shi
Japan	Investigational Site Number 392020	Toyonaka-Shi
Japan	Investigational Site Number 392022	Yao-Shi

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Teramoto T, Kondo A, Kiyosue A, Harada-Shiba M, Ishigaki Y, Tobita K, Kawabata Y, Ozaki A, Baccara-Dinet MT, Sata M. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids Health Dis. 2017 Jun 17;16(1):121. doi: 10.1186/s12944-017-0513-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change From Baseline in Calculated LDL-C at Week 20, 24, 36, 48 and 64 -OLTP Analysis		Baseline, Weeks 20, 24, 36, 48 and 64
Primary	Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis	Adjusted Least-squares (LS) means and standard errors at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were used in the model (ITT analysis).	From Baseline to Week 12
Secondary	Percent Change From Baseline in Calculated LDL-C at Week 12- On-Treatment Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).	From Baseline to Week 12
Secondary	Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12: ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment and assigning a weight of 0.5 for Week 10 and 12 time points.	From Baseline to Week 12
Secondary	Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12- On-Treatment Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection) and assigning a weight of 0.5 for Week 10 and 12 time points.	From Baseline to Week 12
Secondary	Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 12: ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.	From Baseline to Week 12
Secondary	Percent Change From Baseline in Apo-B at Week 12- On-Treatment Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data at from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).	From Baseline to Week 12
Secondary	Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12: ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.	From Baseline to Week 12
Secondary	Percent Change From Baseline in Non-HDL-C at Week 12- On-treatment Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).	From Baseline to Week 12
Secondary	Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12- ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.	From Baseline to Week 12
Secondary	Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- ITT Analysis	Calculated LDL-C goal was defined as calculated LDL-C <100 mg/dL (2.59 mmol/L) for heterozygous familiar hypercholesterolemia (heFH) participants or non-familial hypercholesterolemia (non-FH) participants who had a history of documented CHD, or <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were included in the imputation model.	Up to Week 12
Secondary	Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- On-Treatment Analysis	Calculated LDL-C goal was defined as calculated LDL-C <100 mg/dL (2.59 mmol/L) for heFH participants or non-FH participants who had a history of documented CHD, or <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).	Up to Week 12
Secondary	Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis	Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were included in the imputation model.	From Baseline to Week 12
Secondary	Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12- ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.	From Baseline to Week 12
Secondary	Percent Change From Baseline in Fasting Triglycerides (TGs) at Week 12: ITT Analysis	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.	From Baseline to Week 12
Secondary	Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 12: ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.	From Baseline to Week 12