A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI

Phase 2

Terminated

• Conditions: Microvascular Coronary Artery Disease
• Interventions: Drug: Placebo; Drug: SAR407899; Drug: Adenosine; Drug: Regadenoson; Drug: 13N-ammonia; Drug: 82Rubidium

• Registration Number: NCT03236311
• Lead Sponsor: Sanofi

Brief Summary

Primary Objective:

To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI).

Secondary Objectives:

* To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation scale (SAQ-PL) in participants with MVA and/or persistent stable angina despite angiographically successful PCI.

* To assess the safety of SAR407899 in participants with MVA and/or persistent stable angina despite angiographically successful PCI with a focus on identified risks such as hypotension and orthostatic hypotension.

* To assess SAR407899 plasma concentrations in MVA participants and/or persistent stable angina despite angiographically successful PCI.

Detailed Description

The total duration of study per participant was:

- up to 9 weeks for participants with previous coronary artery angiography or coronary computed tomography angiography (CCTA) within 24 months prior to screening with up to 4 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration.

or

- up to 11 weeks for participants with previous coronary artery angiography or CCTA between 24 months and 5 years prior to screening who need CCTA during screening period with up to 6 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration.

Study Timeline

• Study First Submitted: 2017-07-24
• Study First Submitted QC: 2017-07-31
• Study First Posted: 2017-08-01
• Study Start: 2017-10-12
• Primary Completion: 2018-07-23
• Study Completion: 2018-07-23
• Results First Submitted: 2019-06-17
• Results First Submitted QC: 2019-06-17
• Results First Posted: 2019-07-11
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-15
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo for 4 weeks.
Placebo	Adenosine	Matching placebo for 4 weeks.
SAR407899	13N-ammonia	SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
Placebo	13N-ammonia	Matching placebo for 4 weeks.
Placebo	82Rubidium	Matching placebo for 4 weeks.
SAR407899	82Rubidium	SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
SAR407899	SAR407899	SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
Placebo	Regadenoson	Matching placebo for 4 weeks.
SAR407899	Regadenoson	SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
SAR407899	Adenosine	SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4	Baseline, Week 4	Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4	Baseline, Week 4	The SAQ-PL measures how common daily activities representing low, medium, and high exertional requirements were limited by angina (9 items). It was scored by assigning each response an ordinal value, beginning with 1 for the response that implied the 'lowest level of functioning' to 5 for 'not at all limited', and summing across the 9 items. The score of 9 items was then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. The range of scores was 0 to 100, with higher scores indicates better functioning. A change of 10 points was considered to be clinically important.
Pharmacokinetic Parameter: SAR407899 Plasma Concentration	Day 1, 8, 15, 22, and Day 29

Trial Locations

Locations (10)

Investigational Site Number 8400001; 🇺🇸 Jacksonville, Florida, United States

Investigational Site Number 8400013; 🇺🇸 Wellington, Florida, United States

Investigational Site Number 2080001; 🇩🇰 København Nv, Denmark

Investigational Site Number 8400003; 🇺🇸 Los Angeles, California, United States

Investigational Site Number 7520001; 🇸🇪 Lund, Sweden

Investigational Site Number 5280001; 🇳🇱 Nijmegen, Netherlands

Investigational Site Number 8400010; 🇺🇸 Philadelphia, Pennsylvania, United States

Investigational Site Number 4100002; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 8400006; 🇺🇸 Boston, Massachusetts, United States

Investigational Site Number 8400008; 🇺🇸 Baltimore, Maryland, United States