A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity. (DIRECTION)

A Multicentre, Interventional, Post-marketing, Randomised, Double-blind, Crossover Study to Evaluate the Clinical Safety and Efficacy of AbobotulinumtoxinA (Dysport®) in Comparison With OnabotulinumtoxinA (Botox®) When Treating Adults With Upper Limb Spasticity

This study is aiming to demonstrate the non-inferiority of AbobotulinumtoxinA (aboBoNT-A) versus OnabotulinumtoxinA (onaBoNT-A) as the primary safety endpoint, and the superiority of aboBoNT-A over onaBoNT-A with respect to duration of response as the key secondary efficacy endpoint when used at optimal doses according to approved prescribing information of each product.

Study Overview

• Status: Completed
• Conditions: Upper Limb Spasticity
• Intervention / Treatment: Biological: AboBoNT-A; Biological: OnaBoNT-A

• Study Type: Interventional
• Enrollment (Actual): 464
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Moncton, Canada, E1C 6Z8
    • Moncton Hospital
  • Montreal, Canada, H3A 2B4
    • Genge Partners
  • Victoria, Canada, V9A 3P2
    • Victoria General Hospital
  • Ontario
    • London, Ontario, Canada, N6C 5J1
      • Lawson Health Research Institute
• France
  • Angers, France, 49100
    • Centre Les Capucins
  • Bordeaux, France, 33000
    • Hopital Pellegrin CHU Bordeaux
  • Marseille, France, 13384
    • Hôpital d'Instruction des Armées Laveran
  • Nantes, France, 44000
    • Hôpital Saint-Jacques (CHU Nantes)
  • Nice, France, 06202
    • Hopital Archet (CHU de Nice)
  • Paris, France, 75010
    • Hopital Fernand Widal
  • Ploemeur, France
    • Centre Mutualiste de Rééducation et de Réadaptation Fonction
  • Poitiers, France, 86000
    • Hôpital Jean Bernard (CHU Poitiers)
  • Rennes, France, 35043
    • Pole Saint Helier
  • Rennes, France, 35033
    • Hôpital Pontchaillou (CHU Rennes)
  • Roscoff, France, 29680
    • Centre de Perharidy
  • Saint-Amand-Montrond, France, 18200
    • Centre Hospitalier de Saint Amand Montrond
  • Saint-Amand-les-Eaux, France, 59230
    • Centre Hospitalier de Saint-Amand-les-Eaux
  • Saint-Genis-Laval, France, 69230
    • Hopital Henry Gabrielle (HCL)
  • Strasbourg, France, 67091
    • Hopitaux Universitaires de Strasbourg
  • Toulouse, France, 31059
    • Hôpital de Rangueil
  • Échirolles, France, 38434
    • Hopital Sud
• Puerto Rico
  • Puerto Rico
    • Santurce, Puerto Rico, Puerto Rico, 00912
      • University of Puerto Rico
• United States
  • Alabama
    • Birmingham, Alabama, United States, 25233
      • University of Alabama
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Movement Disorders Center of Arizona
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Scottsdale Osborn Medical Center
    • Tucson, Arizona, United States, 85724
      • The University of Arizona
  • California
    • Downey, California, United States, 90242
      • Rancho Los Amigos National Rehabilitation Center (RLANRC) - Neurology
    • Fountain Valley, California, United States, 92708
      • Parkinson's & Movement Disorders Institute
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center
    • Loma Linda, California, United States, 92350
      • Loma Linda University Health Care
    • Long Beach, California, United States, 90808
      • Southland Neurologic Institute
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Hasbani And Hasbani Medical Group
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners LLC D/B/A New England Institute for Clinical Research
  • Florida
    • Boca Raton, Florida, United States, 33428
      • First Choice Neurology
    • Tampa, Florida, United States, 33612
      • James A Haley Veterans Hospital
    • Tampa, Florida, United States, 33612
      • University of South Florida Health-Morsani Center for Advanced Healthcare
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University of School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Illinois
    • Chicago, Illinois, United States, 60611-3167
      • Shirley Ryan Ability Lab
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Kansas
    • Overland Park, Kansas, United States, 66211-1358
      • Kansas City Bone and Joint Clinic, P.A. (KCBJ) - Overland Pa
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Healthcare network
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center - University Campus
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • William Beaumont Hospital
    • Grand Blanc, Michigan, United States, 48439
      • Medical Rehabilitation Group, PC
    • Grand Rapids, Michigan, United States, 49503
      • Mary Free Bed Rehabilitation Hospital
    • Grosse Pointe, Michigan, United States, 48230
      • Beaumont Hospital, Grosse Pointe
    • Grosse Pointe, Michigan, United States, 48334
      • Michigan Center of Medical Research
  • Missouri
    • Columbia, Missouri, United States, 65203-3248
      • Rusk Rehabilitation Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Wr-Crcn, Llc
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • Cooper University Health Care
  • New York
    • New York, New York, United States, 10016
      • New York University
    • New York, New York, United States, 10065
      • Weill Cornell Medicine Clinical and Translational Science Center
    • Port Jefferson, New York, United States, 11725
      • North Suffolk Neurology
    • Rochester, New York, United States, 55905
      • Mayo Clinic
    • Schenectady, New York, United States, 12308
      • Sunnyview Rehabilitation Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Neurological Institute
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 20010
      • MossRehab - Einstein Medical Center
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Physical Medicine and Rehabilitation - Neurology
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC)
    • Wayne, Pennsylvania, United States, 19087
      • Aether Medicine
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Siskin Hospital for Rehabilitation - Neurology
    • Nashville, Tennessee, United States, 37232
      • The Vanderbilt Clinic
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Houston, Texas, United States, 77030
      • TIRR Memorial Hermann Research Center
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
    • Sherman, Texas, United States, 75093
      • Texas Institute for Neurological Disorders
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Carilion Clinic Institute of Orthopaedics and Neurosciences
  • Washington
    • Columbia, Washington, United States, 20010
      • MedStar National Rehabilitation Network
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent
• 2a. [US/France] Participants with stable Upper Limb Spasticity (ULS) for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study;
• 2b. [Canada] Participants with stable post-stroke ULS for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study
• Participants who are either naïve to Botulinum toxin type A (BoNT-A) for ULS or who have been previously treated with BoNT-A for ULS;
• Participants with MAS score of at least 2 at two muscle groups (one of these two muscles groups should be the PTMG) and at least 1 in the remaining muscle group.
• Participants with DAS score of at least 2 on the Principal Target of Treatment (PTT) (one of four functional domains: dressing, hygiene, limb position and pain);
• Participants who require BoNT-A injection in all of the following muscles: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, flexor digitorum superficialis and biceps brachii;
• Participants for whom injection of a total dose of 900 Units aboBoNT-A or 360 Units onaBoNT-A is considered by the investigator to be clinically appropriate;

• Participants who have been stable for at least 3 months prior to study entry in terms of oral antispasticity, anticoagulant and/or anticholinergic medication if treated are considered by the investigator likely to remain stable for the duration of the study;

  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male participants: Male participants must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception. The participants must agree to use the contraception during the whole period of the study.
  • Female participants:A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

• Is a woman of non-childbearing potential, defined as postmenopausal for at least

  1 year; surgical sterilisation at least 3 months before entering the study; or hysterectomy. or

• Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method during the entire study period.A WOCBP must have a negative highly sensitive pregnancy test at screening (urine or serum) as required by local regulations.

Exclusion Criteria:

• Major limitations in the passive range of motion in the paretic upper limb;
• Major neurological impairment (other than limb paresis) that could negatively affect functional performance;
• Participants clinically requiring injection into any upper limb muscles other than the five muscles of one arm listed in Section 5.1, or requiring injection into both arms or any lower limb within the timeframe of the study;
• Hypersensitivity to any BoNT product or excipients;
• Hypersensitivity to cow's milk protein (casein);
• Infection at the proposed injection site(s);
• Known peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g. myasthenia gravis or Lambert-Eaton syndrome);

• Any medical condition (including dysphagia or breathing difficulties/compromised respiratory function) that in the opinion of the investigator, might jeopardize the participant's safety;

  • abnormal screening/baseline findings or any other medical condition(s) that, in the opinion of the investigator, might jeopardise the participant's safety

• Women who are pregnant or lactating

  • In the clinical judgement of the investigator, BoNT treatment is inappropriate
  • BoNT naïve participants with a history of facial neurogenic disorder (facial paralysis, polyradiculoneuropathy) (only for France)
• Participants treated with BoNT of any type for any indication (e.g. bladder injection, headache or cosmetic) within the previous 12 weeks or planned/likely to be treated during the course of the study;
• Prior history of non-responsiveness to BoNT treatment;
• Previous surgery, or administration of alcohol or phenol in the study limb 6 months or earlier from study enrolment or planned/likely to be treated during the course of the study;
• Participants treated with intrathecal baclofen (except if treatment has reached a stable dose for >4 weeks and is likely to remain stable throughout the study), aminoglycosides or other agents interfering with neuromuscular transmission (e.g. curare-like agents) within the 4 weeks prior to study enrolment or planned/likely to be treated during the course of the study

• Participants receiving concomitant medication treatment with the following PT/OT interventions on the study limb: new splinting/orthotics/casting, serial casting, shockwave therapy, dry needling and needle tenotomies. However, PT/OT interventions not intended to reduce study limb spasticity (e.g. functional training exercises) or with a transient (<1 day) reduction of study limb spasticity (e.g. stretching, weight bearing) are allowed.

  • Participants previously randomised for this study
  • Participants unwilling or unable to understand the nature, scope and possible consequences of the study and to comply with study procedures and requirements
  • Participants currently enrolled in any other clinical study or have participated in one within the 12 weeks (or 5 half-lives of the investigational product of that study, whichever is longer) prior to enrolment/inclusion visit, or are scheduled to receive a new investigational drug while the study is ongoing

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence 1; Participants will receive one cycle of aboBoNT-A followed by one cycle of onaBoNT-A in the selected overactive upper limb muscles	Biological: AboBoNT-A; AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL); Other Names: Dysport®; Biological: OnaBoNT-A; OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL); Other Names: Botox®
Other: Sequence 2; Participants will receive one cycle of onaBoNT-A followed by one cycle of aboBoNT-A in the selected overactive upper limb muscles	Biological: AboBoNT-A; AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL); Other Names: Dysport®; Biological: OnaBoNT-A; OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL); Other Names: Botox®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From Injection to 12 Weeks	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A TEAE was defined for each treatment cycle as any AE that occurred during the cycle if it was not present prior to treatment injection, or it was present prior to treatment injection but the intensity increased during the cycle. Percentage of participants with TEAEs that occurred during each cycle from injection to 12 weeks after injection (until 84 days after injection or until the day prior to next injection day or until end of study/early withdrawal day whichever occurred first) is presented. Percentages are rounded off to the tenth decimal place.	From Baseline (Injection: Day 1) up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Drug Reactions (ADRs), Treatment-Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) From Injection to 12 Weeks	AE: any untoward medical occurrence in a clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via an authorized medicinal product, or any other medically important event. TEAE for each treatment cycle: any AE that occurred during cycle if it was not present prior to treatment injection, or it was present prior to treatment injection but intensity increased during cycle. ADR: any TEAE that was assessed by Investigator as related to study treatment. AESI: TEAE that suggested a possible remote spread of toxin or events suggestive of hypersensitivity like reactions.	From Baseline (Injection: Day 1) up to 12 weeks
Adjusted Least Square Mean of Duration of Response Based on Retreatment Criteria	The duration of response was defined for Cycle 1 as time between Cycle 1 injection and the first Cycle 1 visit when retreatment criteria were met (from Week 10 visit), or time between Cycle 1 injection and study withdrawal if the participant discontinued from the study before Cycle 2 injection without meeting retreatment criteria; for Cycle 2 as time between Cycle 2 injection and the first Cycle 2 visit when retreatment criteria were met (from Week 10 visit), or time between Cycle 2 injection and end of study if the participant completed the study or discontinued from the study after Cycle 2 injection without meeting retreatment criteria. It was calculated as the date of retreatment criteria met or withdrawal date (or last visit date for lost to follow-up participants) or completion date - date of injection + 1.	Baseline (Day 1) up to Week 10 (earliest) if retreatment criteria were met, or up to Week 24 (latest) if retreatment criteria were not met
Adjusted Least Square Mean of Muscle Tone Assessed by the Modified Ashworth Scale (MAS) for Finger, Wrist and Elbow Flexors Based on Primary Target Muscle Group (PTMG) at Week 12	Muscle tone for finger, wrist, elbow flexors assessed with MAS tool using scale: 0= no increase in muscle tone, 1= slight increase in muscle tone, manifested by a catch and release or by minimal resistance at end of range of motion (ROM) when affected part(s) was moved in flexion or extension, 1+= slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout remainder of ROM, 2= more marked increase in muscle tone through most of ROM, but affected part(s) easily moved, 3= considerable increase in muscle tone, passive movement difficult, 4= affected part(s) rigid in flexion or extension. PTMG included finger, wrist or elbow flexors which were selected by Investigators at screening as muscle group with highest MAS score. MAS total score was calculated as the sum of scores for all 3 joints (finger, wrist, elbow), ranged from: 0 (best) to 12 (worst); higher scores indicated worse outcomes.	Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Adjusted Least Square Mean of Perceived Function and Pain Assessed by the Disability Assessment Scale (DAS) Based on Principal Target of Treatment (PTT) at Week 12	The DAS was used to determine the extent of functional impairment in 4 domains: hygiene, dressing, limb position and pain. Impairment was assessed on a 4-point scale: 0= no disability, 1= mild disability (noticeable but did not interfere significantly with normal activities), 2= moderate disability (normal activities required increased effort and/or assistance) and 3= severe disability (normal activities limited). The 4 domain ratings were added to obtain DAS total score which ranged between 0 (best) and 12 (worst); higher scores indicated severe disability. The PTT was defined at screening as 1 of the 4 domains, with an associated DAS score for assessment.	Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Adjusted Least Square Mean of Physician Global Assessment (PGA) of Treatment Response at Week 12	The PGA of treatment response was assessed by asking the Investigator the following question: 'how would you rate the response to treatment in the participant's upper limb since the last injection?' and answered on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). Higher scores indicate greater better outcomes. 'Any improvement' in PGA was defined by a score including: +1, +2, +3 and +4.	Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Change From Baseline to Weeks 4, 12 and 24 (End of Cycle) in Quality of Life (QoL) Assessed by the 12-Item Short Form (SF-12) Health Survey Perceived Health Score: Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) Scores	SF-12 consisted of 12 questions & asked respondent to answer questions as they pertained to way he/she felt or acted during past week. SF-12 covered 8 domains of health:physical functioning(PF),role physical(RP),bodily pain(BP),general health(GH),vitality(VT),social functioning(SF),role emotional(RE) & mental health(MH). Score range for each of 8 domains:0(maximum disability) to 100(no disability);higher scores:good QoL. Responses on SF-12 were used to obtain 2 summary scores:PCS-12 contributed by PF,RP,BP, and GH and MCS-12 contributed by MH,RE,SF and VT. Summations of item scores of same domains gave sub-scale scores,which were transformed to obtain summary scores of PCS-12 & MCS-12. Both PCS-12 & MCS-12 scores ranged from 0(worst) to 100(best);higher scores:better QoL.Baseline:last non-missing measurement prior to first study treatment administration.Change from baseline in QoL assessed by SF-12 health survey perceived health score based on PCS-12 and MCS-12 scores is presented.	Baseline (Day 1) and Weeks 4, 12, and 24 (end of cycle) (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Change From Baseline to Weeks 4, 12 and 24 (End of Cycle) in Quality of Life Assessed by the Spasticity-Related Quality of Life Tool (SQoL-6D)	The SQoL-6D questionnaire was a brief questionnaire in 6 domains: pain/discomfort, involuntary movements or spasms, restricted range of movement, caring for the affected limb, using the affected limb and mobility/balance which was designed to assess QoL in relation to spasticity that affected the upper limb, which included the arm, shoulder or hand. Each dimension was assessed by asking participants about symptoms within the last 7 days, using a 5-level scale ranging from 0 (best) to 4 (worst); higher scores indicated worse condition. The mean of the 6-dimension scores was calculated to obtain the total score which ranged from 0 (worse) to 100 (best); higher score indicated better QoL. Baseline was defined as the last non-missing measurement prior to first study treatment administration. Change from Baseline in QoL assessed by SQoL-6D is presented.	Baseline (Day 1) and Weeks 4, 12, and 24 (end of Cycle) (Cycles 1 and 2; each cycle was 12 to 24 weeks)

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Publications and helpful links

General Publications

• Esquenazi A, Ayyoub Z, Verduzco-Gutierrez M, Maisonobe P, Otto J, Patel AT. AbobotulinumtoxinA Versus OnabotulinumtoxinA in Adults with Upper Limb Spasticity: A Randomized, Double-Blind, Crossover Study Protocol. Adv Ther. 2021 Nov;38(11):5623-5633. doi: 10.1007/s12325-021-01896-3. Epub 2021 Sep 25.
• Esquenazi A, Wein TH, Verduzco-Gutierrez M, Ayyoub Z, Page S, Harding S, Maisonobe P, Beneteau M, Patel A; DIRECTION study group. A Phase IV, Randomized, Double-Blind, Crossover Study to Compare the Clinical Safety and Efficacy of AbobotulinumtoxinA and OnabotulinumtoxinA in Adult Upper Limb Spasticity. Adv Ther. 2026 May 20. doi: 10.1007/s12325-026-03635-y. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2021
• Primary Completion (Actual): August 26, 2025
• Study Completion (Actual): August 26, 2025

Study Registration Dates

• First Submitted: June 9, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Muscle Spasticity; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Metalloproteases; Bacterial Proteins; Bacterial Toxins; Toxins, Biological; Botulinum Toxins, Type A; abobotulinumtoxinA; onabotulinum toxin A
• Other Study ID Numbers: CLIN-52120-452; 2021-000161-32 (EudraCT Number); 2023-509196-16-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.
• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No