A Study Assessing the Efficacy and Safety of Sarilumab Added to MTX in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis (SARIL-RA-KAKEHASI)

A Randomized, Double-blind, Multicenter Study With a Placebo-controlled Period Assessing the Efficacy and Safety of Sarilumab Added to Methotrexate (MTX) in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

Primary Objective:

-To demonstrate that sarilumab added to methotrexate (MTX) reduce signs and symptoms of rheumatoid arthritis (RA) in Japanese RA participants with an inadequate response to MTX.

Secondary Objective:

-To assess the safety of sarilumab added to MTX in Japanese RA participants with an inadequate response to MTX.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Sarilumab SAR153191 (REGN88); Drug: Methotrexate; Drug: Folic acid; Other: Placebo (for sarilumab)

Detailed Description

The total duration of study was expected up to 62 weeks (screening period of 4 weeks, treatment period of 52 weeks, and a 6-week post treatment observation).

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Asahi-Shi, Japan
    • Investigational Site Number 392010
  • Asahikawa-Shi, Japan
    • Investigational Site Number 392001
  • Asahikawa-Shi, Japan
    • Investigational Site Number 392035
  • Beppu-Shi, Japan
    • Investigational Site Number 392070
  • Chiba-Shi, Japan
    • Investigational Site Number 392036
  • Chuo-Ku, Japan
    • Investigational Site Number 392083
  • Fuchu-Shi, Japan
    • Investigational Site Number 392047
  • Fukui-Shi, Japan
    • Investigational Site Number 392004
  • Fukuoka-Shi, Japan
    • Investigational Site Number 392007
  • Fukuoka-Shi, Japan
    • Investigational Site Number 392038
  • Fukuoka-Shi, Japan
    • Investigational Site Number 392039
  • Fukushima-Shi, Japan
    • Investigational Site Number 392078
  • Funabashi-Shi, Japan
    • Investigational Site Number 392054
  • Hachioji-Shi, Japan
    • Investigational Site Number 392015
  • Hannan-Shi, Japan
    • Investigational Site Number 392085
  • Hiroshima-Shi, Japan
    • Investigational Site Number 392091
  • Hiroshima-Shi, Japan
    • Investigational Site Number 392098
  • Hitachinaka-Shi, Japan
    • Investigational Site Number 392009
  • Hitachinaka-Shi, Japan
    • Investigational Site Number 392011
  • Ichinomiya-Shi, Japan
    • Investigational Site Number 392030
  • Iizuka-Shi, Japan
    • Investigational Site Number 392002
  • Kagoshima-Shi, Japan
    • Investigational Site Number 392019
  • Kamakura-Shi, Japan
    • Investigational Site Number 392066
  • Kamogawa-Shi, Japan
    • Investigational Site Number 392086
  • Kato-Shi, Japan
    • Investigational Site Number 392050
  • Kawachi-Nagano-Shi, Japan
    • Investigational Site Number 392037
  • Kawagoe-Shi, Japan
    • Investigational Site Number 392093
  • Kawasaki-Shi, Japan
    • Investigational Site Number 392099
  • Kirishima-Shi, Japan
    • Investigational Site Number 392016
  • Kitakyushu-Shi, Japan
    • Investigational Site Number 392013
  • Kitakyushu-Shi, Japan
    • Investigational Site Number 392024
  • Kitakyushu-Shi, Japan
    • Investigational Site Number 392045
  • Kiyose-Shi, Japan
    • Investigational Site Number 392063
  • Kobe-Shi, Japan
    • Investigational Site Number 392051
  • Kochi-Shi, Japan
    • Investigational Site Number 392097
  • Koushi-Shi, Japan
    • Investigational Site Number 392040
  • Kumamoto-Shi, Japan
    • Investigational Site Number 392069
  • Kurashiki-Shi, Japan
    • Investigational Site Number 392089
  • Kushiro-Shi, Japan
    • Investigational Site Number 392065
  • Matsuyama-Shi, Japan
    • Investigational Site Number 392026
  • Matsuyama-Shi, Japan
    • Investigational Site Number 392081
  • Matsuyama-Shi, Japan
    • Investigational Site Number 392094
  • Meguro-Ku, Japan
    • Investigational Site Number 392042
  • Meguro-Ku, Japan
    • Investigational Site Number 392082
  • Mito-Shi, Japan
    • Investigational Site Number 392012
  • Miyagi-Gun, Japan
    • Investigational Site Number 392034
  • Morioka-Shi, Japan
    • Investigational Site Number 392053
  • Nagano-Shi, Japan
    • Investigational Site Number 392032
  • Nagasaki-Shi, Japan
    • Investigational Site Number 392064
  • Nagoya-Shi, Japan
    • Investigational Site Number 392043
  • Nagoya-Shi, Japan
    • Investigational Site Number 392056
  • Nagoya-Shi, Japan
    • Investigational Site Number 392076
  • Nagoya-Shi, Japan
    • Investigational Site Number 392080
  • Nakano-Ku, Japan
    • Investigational Site Number 392031
  • Narashino-Shi, Japan
    • Investigational Site Number 392046
  • Narashino-Shi, Japan
    • Investigational Site Number 392067
  • Nishinomiya-Shi, Japan
    • Investigational Site Number 392044
  • Oita-Shi, Japan
    • Investigational Site Number 392059
  • Okayama-Shi, Japan
    • Investigational Site Number 392062
  • Omura-Shi, Japan
    • Investigational Site Number 392008
  • Osaka-Shi, Japan
    • Investigational Site Number 392057
  • Osaka-Shi, Japan
    • Investigational Site Number 392060
  • Osaka-Shi, Japan
    • Investigational Site Number 392061
  • Osaka-Shi, Japan
    • Investigational Site Number 392096
  • Osaki-Shi, Japan
    • Investigational Site Number 392027
  • Sagamihara-Shi, Japan
    • Investigational Site Number 392049
  • Saitama-Shi, Japan
    • Investigational Site Number 392072
  • Sakai-Shi, Japan
    • Investigational Site Number 392075
  • Sapporo-Shi, Japan
    • Investigational Site Number 392014
  • Sapporo-Shi, Japan
    • Investigational Site Number 392068
  • Sapporo-Shi, Japan
    • Investigational Site Number 392073
  • Sasebo-Shi, Japan
    • Investigational Site Number 392006
  • Sendai-Shi, Japan
    • Investigational Site Number 392021
  • Sendai-Shi, Japan
    • Investigational Site Number 392022
  • Sendai-Shi, Japan
    • Investigational Site Number 392033
  • Sendai-Shi, Japan
    • Investigational Site Number 392071
  • Sendai-Shi, Japan
    • Investigational Site Number 392100
  • Shizuoka-Shi, Japan
    • Investigational Site Number 392029
  • Sumida-Ku, Japan
    • Investigational Site Number 392025
  • Sumida-Ku, Japan
    • Investigational Site Number 392092
  • Takaoka-Shi, Japan
    • Investigational Site Number 392023
  • Takarazuka-Shi, Japan
    • Investigational Site Number 392095
  • Takasaki-Shi, Japan
    • Investigational Site Number 392020
  • Takatsuki-Shi, Japan
    • Investigational Site Number 392088
  • Tokorozawa-Shi, Japan
    • Investigational Site Number 392018
  • Tomakomai-Shi, Japan
    • Investigational Site Number 392003
  • Tomakomai-Shi, Japan
    • Investigational Site Number 392005
  • Tonami-Shi, Japan
    • Investigational Site Number 392077
  • Toshima-Ku, Japan
    • Investigational Site Number 392052
  • Toyama-Shi, Japan
    • Investigational Site Number 392058
  • Toyonaka-Shi, Japan
    • Investigational Site Number 392055
  • Urasoe-Shi, Japan
    • Investigational Site Number 392074
  • Urayasu-Shi, Japan
    • Investigational Site Number 392079
  • Yokohama-Shi, Japan
    • Investigational Site Number 392048
  • Yokohama-Shi, Japan
    • Investigational Site Number 392090
  • Yokohama-Shi, Japan
    • Investigational Site Number 392101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Diagnosis of RA, according to the American College of Rheumatology/The European League Against Rheumatism (ACR/EULAR) 2010 Rheumatoid Arthritis Classification Criteria with >=3 months disease duration.
• Moderately to severely active RA defined as:
• At least 8 of 68 tender joints and 6 of 66 swollen joints at screening visit.
• High sensitivity C-Reactive Protein (hs-CRP) >=6mg/L at screening visit.

Exclusion criteria:

• Participants <20 or >75 years of age.
• Treatment with any Disease-modifying antirheumatic drug (DMARD) other than MTX or biologic agent without the appropriate off-drug period prior to screening.
• Prior treatment with anti-interleukin-6 (anti-IL-6) or anti-interleukin-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sarilumab 150 mg/150 mg; Sarilumab 150 mg subcutaneous (SC) injection once every 2 weeks (q2w) in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either tender joint count [TJC] or swollen joint count [SJC], or with any other clear lack of efficacy based on investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.	Drug: Sarilumab SAR153191 (REGN88); Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Methotrexate; Dispensed according to local practice.; Drug: Folic acid; Dispensed according to local practice.
Experimental: Sarilumab 200 mg/200 mg; Sarilumab 200 mg SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by single-blind period in which participants continued with the same treatment up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either TJC or SJC, or with any other clear lack of efficacy based on investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.	Drug: Sarilumab SAR153191 (REGN88); Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Methotrexate; Dispensed according to local practice.; Drug: Folic acid; Dispensed according to local practice.
Placebo Comparator: Placebo/Sarilumab 150 mg; Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 150 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.	Drug: Sarilumab SAR153191 (REGN88); Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Methotrexate; Dispensed according to local practice.; Drug: Folic acid; Dispensed according to local practice.; Other: Placebo (for sarilumab); Pharmaceutical form: solution for injection Route of administration: subcutaneous
Placebo Comparator: Placebo/Sarilumab 200 mg; Placebo (for sarilumab) SC injection q2w in combination with MTX and folic acid in double-blind period up to Week 24 followed by a single-blind period in which participants were switched and received sarilumab 200 mg SC injection q2w in combination with MTX and folic acid up to Week 52. Participants with inadequate response (defined as less than 20% improvement from baseline on 2 consecutive visits [at least 4 weeks apart] in either TJC or SJC, or with any other clear lack of efficacy based on Investigator's judgment) by Week 16, were rescued with open label sarilumab 200 mg q2w treatment.	Drug: Sarilumab SAR153191 (REGN88); Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Methotrexate; Dispensed according to local practice.; Drug: Folic acid; Dispensed according to local practice.; Other: Placebo (for sarilumab); Pharmaceutical form: solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 24	American College of Rheumatology (ACR) response is a composite rating scale that includes 7 variables: tender joints count (TJC [68 joints]); Swollen joints count (SJC [66 joints]); levels of an acute phase reactant (high sensitivity C-reactive protein [hs-CRP level]); participant's assessment of pain (measured on 0 [no pain]-100 mm [worst pain] visual analog scale [VAS]); participant's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); physician's global assessment of disease activity (measured on 0 [no arthritis activity]-100 mm [maximal arthritis activity] VAS); participant's assessment of physical function (measured by health assessment questionnaire disability index [HAQ-DI], with scoring range of 0 [better health] - 3 [worst health]). ACR20 response was defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AEs that developed or worsened or became serious during double-blind on-treatment period, single-blind on-treatment period up to 6-week post-treatment follow-up period (up to Week 58) were considered treatment-emergent.	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities	Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure supine (SBP[S]): <=95 mmHg and decrease from baseline (DFB) >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg; Diastolic blood pressure supine (DBP[S]): <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg; Orthostatic systolic blood pressure (SBP[O]): <=-20 mmHg; Orthostatic diastolic blood pressure (DBP[O]): <=-10 mmHg; Heart rate supine (HR[S]): <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm; Weight: >=5% DFB; >=5% IFB	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities	Criteria for potentially clinically significant ECG abnormalities: PR Interval: >200 millisecond (ms); >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB >=25%; QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%; QT Interval: >500 ms; QTc Bazett (QTc B): >450 ms; 480 ms; 500 ms; IFB >30 and <=60 ms; IFB >60 ms; QTc Fridericia (QTc F): >450 ms; 480 ms; 500 ms; IFB >30 and <=60 ms; IFB >60 ms	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters	Criteria for potentially clinically significant abnormalities: Hemoglobin: <=115 g/L (Male[M]) or <=95 g/L (Female[F]); >=185 g/L (M) or >=165 g/L (F); DFB >=20 g/L; Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F); >=0.55 v/v (M) or >=0.5 v/v (F); Red blood cells (RBC): >=6 Tera/L; Platelets: <50 Giga/L; >=50 and <100 Giga/L; >=700 Giga/L; White blood cells (WBC): <3.0 Giga/L (Non-Black[NB]) or <2.0 Giga/L (Black[B]); >=16.0 Giga/L; Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); <1.0 Giga/L; Lymphocytes: <0.5 Giga/L; >=0.5 Giga/L and < lower limit of normal (LLN); >4.0 Giga/L; Monocytes: >0.7 Giga/L; Basophils: >0.1 Giga/L; Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L)	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters	Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L unfasted or >=7 mmol/L fasted; Hemoglobin A1c (HbA1c): >8%; Total cholesterol: >=6.2 mmol/L; >=7.74 mmol/L; LDL cholesterol: >=4.1 mmol/L; >=4.9 mmol/L; Triglycerides: >=4.6 mmol/L; >=5.6 mmol/L	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes	Criteria for potentially clinically significant abnormalities: Sodium: <=129 mmol/L; >=160 mmol/L; Potassium: <3 mmol/L; >=5.5 mmol/L; Chloride: <80 mmol/L; >115 mmol/L	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters	Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L; >=30% change from baseline; >=100% change from baseline; Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to < 60 mL/min; >=60 to <90 mL/min; Blood urea nitrogen: >=17 mmol/L; Uric acid: <120 micromol/L; >408 micromol/L	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters	Criteria for potentially clinically significant abnormalities: Alanine Aminotransferase (ALT): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN; Aspartate aminotransferase (AST): >1 ULN and <=1.5 ULN; >1.5 ULN and <=3 ULN; >3 ULN and <=5 ULN; >5 ULN and <=10 ULN; >10 ULN and <=20 ULN; >20 ULN; Alkaline phosphatase: >1.5 ULN; Total bilirubin (TBILI): >1.5 ULN; >2 ULN; Conjugated bilirubin (CBILI): >1.5 ULN; >2 ULN; Unconjugated bilirubin: >1.5 ULN; >2 ULN; ALT and TBILI: ALT >3 ULN and TBILI >2 ULN; CBILI and TBILI: CBILI >35% TBILI and TBILI >1.5 ULN; Albumin: <=25 g/L	For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm : Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Tanaka Y, Takahashi T, Van Hoogstraten H, Praestgaard A, Kato N, Kameda H. Haemoglobin changes and disease activity in Japanese patients with rheumatoid arthritis treated with sarilumab. Clin Exp Rheumatol. 2022 Oct 28. doi: 10.55563/clinexprheumatol/jq9u8f. Online ahead of print.
• Tanaka Y, Wada K, Takahashi Y, Hagino O, van Hoogstraten H, Graham NMH, Kameda H. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan. Arthritis Res Ther. 2019 Mar 20;21(1):79. doi: 10.1186/s13075-019-1856-4. Erratum In: Arthritis Res Ther. 2019 Apr 16;21(1):99.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: November 18, 2014
• First Posted (Estimate): November 19, 2014

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Micronutrients; Vitamins; Reproductive Control Agents; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Folic Acid
• Other Study ID Numbers: EFC14059; U1111-1155-7401 (Other Identifier: UTN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: Yes