Broad-spectrum Rapid Antidote: Varespladib Oral for Snakebite

NCT04996264 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: OPX-PR-01
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 16

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study designed to evaluate the safety, tolerability and efficacy of varespladib-methyl, concurrently with standard of care (SOC), in subjects bitten by venomous snakes.

Conditions

Snakebites; Envenoming; Envenoming, Snake; Envenomation, Snake

Keywords

envenoming; venom; snakebite; snakebite severity score; varespladib; snake; antidote; LY333013; sPLA2

Outcome Measures

Primary Outcomes (1)

• Change in the Combined Pulmonary, Cardiovascular, Hematologic, Nervous System, and Renal Subscores of the Snakebite Severity Score (SSS)

  Change from baseline (pre-dosing) to 6 and 9 hours after the first dose, in the combined pulmonary, cardiovascular, hematologic symptoms, nervous system, and renal subscores of the SSS. The values from each of these subscores will be totaled. The average of the 6- and 9-hour scores will be used as the post-treatment value. The Snakebite Severity Scale (SSS) is a tool used to measure the severity of envenoming based on up to 7 body categories: pulmonary, cardiovascular, gastrointestinal, nervous, and renal system (graded at levels from Grade 0 to Grade 3), local wound, and hematological, (graded at levels from Grade 0 to Grade 4). A higher score indicates worse symptoms. The minimum score for the five item SSS is 0 and the maximum score is 16, with the higher score indicating worse symptoms. For the primary outcome we are focusing only on 5 subscores, that does not include the local wound nor the gastrointestinal subscores.

  Baseline to 6 and 9 hours after first dose

Secondary Outcomes (6)

• Area Under the Curve (AUC) of the Local Wound, Pulmonary, Cardiovascular, Hematologic Symptoms, Renal, and Nervous System Sections of the SSS

  Baseline through Day 7

• Area Under the Curve (AUC) of the Numeric Pain Rating Scale (NPRS)

  From Baseline through Day 3

• Clinician Global Impression - Improvement

  Day 2

• All-cause Mortality

  Baseline through Day 28

• Patient-Specific Functional Scale (PSFS) Score

  Day 7

Other Outcomes (1)

• Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation of Investigational Product (IP)

  28 Days after the initiation of study drug

Study Arms (2)

Varespladib-methyl

EXPERIMENTAL

Varespladib-methyl is an immediate-release (IR), oval, white, film-coated tablet at a dosage strength of 250 mg for oral administration. Scaled pediatric doses of varespladib-methyl are supplied as 50 mg IR capsules for oral administration. Adult subjects will receive an initial loading dose of 500 mg (2 × 250 mg oral tablet) varespladib-methyl upon randomization, followed by dosing with 250 mg varespladib-methyl (1 × 250 mg oral tablet) approximately 12 hours later, and subsequent twice daily (BID) dosing with 1 × 250 mg varespladib-methyl oral tablets for the remainder of the 7-day treatment period. Tablets may be administered via naso- or orogastric tubes in patients requiring mechanical ventilation. Pediatric subjects (5 to \< 18 years) will be administered doses of varespladib-methyl determined by allometric scaling, provided as 50 mg capsules. Age-appropriate capsules may be administered via naso- or orogastric tubes in patients requiring mechanical ventilation.

Drug: Varespladib Methyl; Drug: Standard of care (SOC)

Placebo

PLACEBO COMPARATOR

The oral placebo is supplied as a white film-coated oval tablet to match the appearance of the varespladib-methyl 250 mg tablet and contains a subset of the excipients present in the active tablet formulation: lactose monohydrate, microcrystalline cellulose, and magnesium stearate. Placebo for scaled pediatric dosing is supplied as an immediate-release capsule to match the varespladib-methyl 50 mg capsule, and contains the excipients lactose monohydrate, microcrystalline cellulose, and magnesium stearate. The dosing of placebo will match that of varespladib-methyl.

Drug: Placebo; Drug: Standard of care (SOC)

Interventions

Varespladib Methyl DRUG

Varespladib-methyl (LY333013) is an IR, oval, white, film-coated tablet at a dosage strength of 250 mg for oral administration. Scaled pediatric doses of varespladib-methyl (LY333013) are supplied as 50 mg IR capsules for oral administration.

Also known as: LY333013

Varespladib-methyl

Placebo DRUG

The oral placebo is supplied as a white film-coated oval tablet to match the appearance of the varespladib-methyl 250 mg tablet and contains a subset of the excipients present in the active tablet formulation: lactose monohydrate, microcrystalline cellulose, and magnesium stearate. Placebo for scaled pediatric dosing is supplied as an IR capsule to match the varespladib-methyl 50 mg capsule, and contains the excipients lactose monohydrate, microcrystalline cellulose, and magnesium stearate.

Placebo

Standard of care (SOC) DRUG

SOC (including antivenom) will continue to be administered throughout the subject's participation in the study according to the protocol and the judgment of the Investigator.

Placebo; Varespladib-methyl

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Is a male or female subject ≥ 5 years of age with venomous snakebite and must present with an initial SSS of
• points in any SSS category other than gastrointestinal and 1 or more additional points in any other SSS category other than gastrointestinal or
• ≥ 3 in any SSS category other than gastrointestinal.
• Index event (snakebite) must be symptomatic and must have occurred within 10 hours of eligibility assessment.
• Category 1: The patient has not yet completed first dose of antivenom:
• Category 2: The patient has completed an initial dose of antivenom:
• Is willing (or legally authorized representative is willing) to provide informed consent prior to initiation of any study procedures.

You may not qualify if:

• Has received antivenom treatment for envenoming prior to enrollment in this study.
• Is considered by the investigator to have a clinically significant upper GI bleed evidenced by hematemesis, "coffee-ground" emesis or nasogastric aspirate, or hematochezia thought to originate from upper GI tract.
• Has history of cerebrovascular accident or intracranial bleeding of any kind, acute coronary syndrome, myocardial infarction, or severe pulmonary hypertension.
• Has known history of inherited bleeding or coagulation disorder.
• Is, at Screening Visit, using the following anticoagulants: warfarin/coumadin, argatroban, bivalirudin, lepirudin, apixaban, dabigatran, clopidogrel, prasugrel, ticlopidine or another anticoagulant agent not specifically listed, or has used heparin, enoxaparin, fondaparinux, or other low molecular weight heparin or antiarrhythmic drugs within 14 days prior to treatment.
• Has a history of chronic liver disease such as chronic active viral hepatitis, alcohol-related liver disease, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, or autoimmune hepatitis.
• Reports or has known pre-existing renal impairment or chronic kidney disease (defined as Stage 4 or receiving dialysis or hemofiltration).
• Has a known allergy or significant adverse reaction to varespladib-methyl or related compounds.
• Is considered by the Investigator to be unable to comply with protocol requirements due to geographic considerations, psychiatric disorders, or other compliance concerns.
• Is pregnant, has a positive serum human chorionic gonadotropin (hCG) pregnancy test or not willing to use a highly effective method of contraception for 14 days after initial treatment, or is breast-feeding.

Sponsors & Collaborators

• Ophirex, Inc.: lead
• Premier Research: collaborator

Study Sites (16)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

University of Florida Health

Jacksonville, Florida, 32209, United States

Location

Agusta University Medical Center

Augusta, Georgia, 30912, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

LSU LA Poison Control Center

Shreveport, Louisiana, 71103, United States

Location

University of Mississippi Medical Center - Jackson

Jackson, Mississippi, 39216, United States

Location

Duke University Hospital Durham, NC

Durham, North Carolina, 27710, United States

Location

Government medical College

Kozhikode, Calicut, India

Location

Father Muller medical College Hospital

Mangalore, Karnataka, 575002, India

Location

K R Hospital Mysore medical College and Research Institute

Mysore, Karnataka, India

Location

Jubilee Mission Medical College and Research Institute

Thrissur, Kerala, India

Location

Jawaharlal Institute of Postgraduate Medical Education & Research

Puducherry, Puducherry, India

Location

S.P. Medical College Snakebite Research Cell

Bikaner, Rajasthan, India

Location

Calcutta National Medical College

Kolkata, West Bengal, India

Location

Postgraduate Institute of Medical Education and Research

Chandigarh, India

Location

Related Publications (37)

• Varespladib. Am J Cardiovasc Drugs. 2011;11(2):137-43. doi: 10.2165/11533650-000000000-00000.

  PMID: 21446779 BACKGROUND

• Alangode A, Rajan K, Nair BG. Snake antivenom: Challenges and alternate approaches. Biochem Pharmacol. 2020 Nov;181:114135. doi: 10.1016/j.bcp.2020.114135. Epub 2020 Jul 3.

  PMID: 32628928 BACKGROUND

• Albulescu LO, Xie C, Ainsworth S, Alsolaiss J, Crittenden E, Dawson CA, Softley R, Bartlett KE, Harrison RA, Kool J, Casewell NR. A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite. Nat Commun. 2020 Dec 15;11(1):6094. doi: 10.1038/s41467-020-19981-6.

  PMID: 33323937 BACKGROUND

• Anderson BO, Moore EE, Banerjee A. Phospholipase A2 regulates critical inflammatory mediators of multiple organ failure. J Surg Res. 1994 Feb;56(2):199-205. doi: 10.1006/jsre.1994.1032.

  PMID: 8121178 BACKGROUND

• Arce-Bejarano R, Lomonte B, Gutierrez JM. Intravascular hemolysis induced by the venom of the Eastern coral snake, Micrurus fulvius, in a mouse model: identification of directly hemolytic phospholipases A2. Toxicon. 2014 Nov;90:26-35. doi: 10.1016/j.toxicon.2014.07.010. Epub 2014 Aug 1.

  PMID: 25088177 BACKGROUND

• Bittenbinder MA, Zdenek CN, Op den Brouw B, Youngman NJ, Dobson JS, Naude A, Vonk FJ, Fry BG. Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib). Toxins (Basel). 2018 Dec 4;10(12):516. doi: 10.3390/toxins10120516.

  PMID: 30518149 BACKGROUND

• Bryan-Quiros W, Fernandez J, Gutierrez JM, Lewin MR, Lomonte B. Neutralizing properties of LY315920 toward snake venom group I and II myotoxic phospholipases A2. Toxicon. 2019 Jan;157:1-7. doi: 10.1016/j.toxicon.2018.11.292. Epub 2018 Nov 14.

  PMID: 30447275 BACKGROUND

• Bulfone TC, Samuel SP, Bickler PE, Lewin MR. Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite. J Trop Med. 2018 Jul 30;2018:4320175. doi: 10.1155/2018/4320175. eCollection 2018.

  PMID: 30154870 BACKGROUND

• Chippaux JP. Estimate of the burden of snakebites in sub-Saharan Africa: a meta-analytic approach. Toxicon. 2011 Mar 15;57(4):586-99. doi: 10.1016/j.toxicon.2010.12.022. Epub 2011 Jan 9.

  PMID: 21223975 BACKGROUND

• Fernandez ML, Quartino PY, Arce-Bejarano R, Fernandez J, Camacho LF, Gutierrez JM, Kuemmel D, Fidelio G, Lomonte B. Intravascular hemolysis induced by phospholipases A2 from the venom of the Eastern coral snake, Micrurus fulvius: Functional profiles of hemolytic and non-hemolytic isoforms. Toxicol Lett. 2018 Apr;286:39-47. doi: 10.1016/j.toxlet.2017.11.037. Epub 2017 Nov 29.

  PMID: 29197624 BACKGROUND

• Fontana Oliveira IC, Gutierrez JM, Lewin MR, Oshima-Franco Y. Varespladib (LY315920) inhibits neuromuscular blockade induced by Oxyuranus scutellatus venom in a nerve-muscle preparation. Toxicon. 2020 Nov;187:101-104. doi: 10.1016/j.toxicon.2020.08.023. Epub 2020 Sep 2.

  PMID: 32889027 BACKGROUND

• Gerardo CJ, Vissoci JRN, Evans CS, Simel DL, Lavonas EJ. Does This Patient Have a Severe Snake Envenomation?: The Rational Clinical Examination Systematic Review. JAMA Surg. 2019 Apr 1;154(4):346-354. doi: 10.1001/jamasurg.2018.5069.

  PMID: 30758508 BACKGROUND

• Gutierrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA. Snakebite envenoming. Nat Rev Dis Primers. 2017 Sep 14;3:17063. doi: 10.1038/nrdp.2017.63.

  PMID: 28905944 BACKGROUND

• Gutierrez JM, Lewin MR, Williams DJ, Lomonte B. Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. Toxins (Basel). 2020 Feb 20;12(2):131. doi: 10.3390/toxins12020131.

  PMID: 32093386 BACKGROUND

• Halilu S, Iliyasu G, Hamza M, Chippaux JP, Kuznik A, Habib AG. Snakebite burden in Sub-Saharan Africa: estimates from 41 countries. Toxicon. 2019 Mar 1;159:1-4. doi: 10.1016/j.toxicon.2018.12.002. Epub 2018 Dec 27.

  PMID: 30594637 BACKGROUND

• Kazandjian TD, Petras D, Robinson SD, van Thiel J, Greene HW, Arbuckle K, Barlow A, Carter DA, Wouters RM, Whiteley G, Wagstaff SC, Arias AS, Albulescu LO, Plettenberg Laing A, Hall C, Heap A, Penrhyn-Lowe S, McCabe CV, Ainsworth S, da Silva RR, Dorrestein PC, Richardson MK, Gutierrez JM, Calvete JJ, Harrison RA, Vetter I, Undheim EAB, Wuster W, Casewell NR. Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science. 2021 Jan 22;371(6527):386-390. doi: 10.1126/science.abb9303.

  PMID: 33479150 BACKGROUND

• Le Geyt J, Pach S, Gutierrez JM, Habib AG, Maduwage KP, Hardcastle TC, Hernandez Diaz R, Avila-Aguero ML, Ya KT, Williams D, Halbert J. Paediatric snakebite envenoming: recognition and management of cases. Arch Dis Child. 2021 Jan;106(1):14-19. doi: 10.1136/archdischild-2020-319428. Epub 2020 Oct 28.

  PMID: 33115713 BACKGROUND

• Lewin M, Samuel S, Merkel J, Bickler P. Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation. Toxins (Basel). 2016 Aug 25;8(9):248. doi: 10.3390/toxins8090248.

  PMID: 27571102 BACKGROUND

• Lewin MR, Gilliam LL, Gilliam J, Samuel SP, Bulfone TC, Bickler PE, Gutierrez JM. Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom. Toxins (Basel). 2018 Nov 17;10(11):479. doi: 10.3390/toxins10110479.

  PMID: 30453607 BACKGROUND

• Lewin MR, Gutierrez JM, Samuel SP, Herrera M, Bryan-Quiros W, Lomonte B, Bickler PE, Bulfone TC, Williams DJ. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins (Basel). 2018 Sep 20;10(10):380. doi: 10.3390/toxins10100380.

  PMID: 30241297 BACKGROUND

• Longbottom J, Shearer FM, Devine M, Alcoba G, Chappuis F, Weiss DJ, Ray SE, Ray N, Warrell DA, Ruiz de Castaneda R, Williams DJ, Hay SI, Pigott DM. Vulnerability to snakebite envenoming: a global mapping of hotspots. Lancet. 2018 Aug 25;392(10148):673-684. doi: 10.1016/S0140-6736(18)31224-8. Epub 2018 Jul 17.

  PMID: 30017551 BACKGROUND

• Pach S, Le Geyt J, Gutierrez JM, Williams D, Maduwage KP, Habib AG, Gustin R, Avila-Aguero ML, Ya KT, Halbert J. Paediatric snakebite envenoming: the world's most neglected 'Neglected Tropical Disease'? Arch Dis Child. 2020 Dec;105(12):1135-1139. doi: 10.1136/archdischild-2020-319417. Epub 2020 Sep 30.

  PMID: 32998874 BACKGROUND

• PARRISH HM. SNAKE VENENATION IN ILLINOIS. IMJ Ill Med J. 1965 Jun;127:671-7. No abstract available.

  PMID: 14295634 BACKGROUND

• Prasarnpun S, Walsh J, Awad SS, Harris JB. Envenoming bites by kraits: the biological basis of treatment-resistant neuromuscular paralysis. Brain. 2005 Dec;128(Pt 12):2987-96. doi: 10.1093/brain/awh642. Epub 2005 Sep 29.

  PMID: 16195243 BACKGROUND

• Ruha AM, Kleinschmidt KC, Greene S, Spyres MB, Brent J, Wax P, Padilla-Jones A, Campleman S; ToxIC Snakebite Study Group. The Epidemiology, Clinical Course, and Management of Snakebites in the North American Snakebite Registry. J Med Toxicol. 2017 Dec;13(4):309-320. doi: 10.1007/s13181-017-0633-5. Epub 2017 Oct 3.

  PMID: 28975491 BACKGROUND

• Salvador GHM, Gomes AAS, Bryan-Quiros W, Fernandez J, Lewin MR, Gutierrez JM, Lomonte B, Fontes MRM. Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920). Sci Rep. 2019 Nov 20;9(1):17203. doi: 10.1038/s41598-019-53755-5.

  PMID: 31748642 BACKGROUND

• Sankar J, Nabeel R, Sankar MJ, Priyambada L, Mahadevan S. Factors affecting outcome in children with snake envenomation: a prospective observational study. Arch Dis Child. 2013 Aug;98(8):596-601. doi: 10.1136/archdischild-2012-303025. Epub 2013 May 28.

  PMID: 23716133 BACKGROUND

• Schulte J, Domanski K, Smith EA, Menendez A, Kleinschmidt KC, Roth BA. Childhood Victims of Snakebites: 2000-2013. Pediatrics. 2016 Nov;138(5):e20160491. doi: 10.1542/peds.2016-0491.

  PMID: 27940763 BACKGROUND

• Seifert SA, Boyer LV, Benson BE, Rogers JJ. AAPCC database characterization of native U.S. venomous snake exposures, 2001-2005. Clin Toxicol (Phila). 2009 Apr;47(4):327-35. doi: 10.1080/15563650902870277.

  PMID: 19514880 BACKGROUND

• Snyder DW, Bach NJ, Dillard RD, Draheim SE, Carlson DG, Fox N, Roehm NW, Armstrong CT, Chang CH, Hartley LW, Johnson LM, Roman CR, Smith AC, Song M, Fleisch JH. Pharmacology of LY315920/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI. J Pharmacol Exp Ther. 1999 Mar;288(3):1117-24.

  PMID: 10027849 BACKGROUND

• Sorensen J, Kald B, Tagesson C, Lindahl M. Platelet-activating factor and phospholipase A2 in patients with septic shock and trauma. Intensive Care Med. 1994 Nov;20(8):555-61. doi: 10.1007/BF01705721.

  PMID: 7706567 BACKGROUND

• Tasoulis T, Isbister GK. A Review and Database of Snake Venom Proteomes. Toxins (Basel). 2017 Sep 18;9(9):290. doi: 10.3390/toxins9090290.

  PMID: 28927001 BACKGROUND

• Uhl W, Beger HG, Hoffmann G, Hanisch E, Schild A, Waydhas C, Entholzner E, Muller K, Kellermann W, Vogeser M, et al. A multicenter study of phospholipase A2 in patients in intensive care units. J Am Coll Surg. 1995 Mar;180(3):323-31.

  PMID: 7874343 BACKGROUND

• Vaiyapuri S, Vaiyapuri R, Ashokan R, Ramasamy K, Nattamaisundar K, Jeyaraj A, Chandran V, Gajjeraman P, Baksh MF, Gibbins JM, Hutchinson EG. Snakebite and its socio-economic impact on the rural population of Tamil Nadu, India. PLoS One. 2013 Nov 21;8(11):e80090. doi: 10.1371/journal.pone.0080090. eCollection 2013.

  PMID: 24278244 BACKGROUND

• Williams DJ, Faiz MA, Abela-Ridder B, Ainsworth S, Bulfone TC, Nickerson AD, Habib AG, Junghanss T, Fan HW, Turner M, Harrison RA, Warrell DA. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Negl Trop Dis. 2019 Feb 21;13(2):e0007059. doi: 10.1371/journal.pntd.0007059. eCollection 2019 Feb. No abstract available.

  PMID: 30789906 BACKGROUND

• Xie C, Albulescu LO, Bittenbinder MA, Somsen GW, Vonk FJ, Casewell NR, Kool J. Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins. Biomedicines. 2020 Aug 20;8(9):297. doi: 10.3390/biomedicines8090297.

  PMID: 32825484 BACKGROUND

• Zinenko O, Tovstukha I, Korniyenko Y. PLA2 Inhibitor Varespladib as an Alternative to the Antivenom Treatment for Bites from Nikolsky's Viper Vipera berus nikolskii. Toxins (Basel). 2020 May 29;12(6):356. doi: 10.3390/toxins12060356.

  PMID: 32485836 BACKGROUND

Related Links

• Drug Development and Drug Interactions \| Table of Substrates, Inhibitors and Inducers

MeSH Terms

Conditions

Snake Bites

Interventions

varespladib methyl; Standard of Care

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Tim Platts-Mills, Chief Medical Officer
• Organization: Ophirex, Inc.

tim@ophirex.com

5592406073

Study Officials

• Matthew Lewin, MD, PhD

  Ophirex, Inc.

  PRINCIPAL INVESTIGATOR

• Timothy F Platts-Mills, MD, MSc

  Ophirex, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All subjects, Investigators, and study personnel involved in the conduct of the study, including data management, will be blinded to treatment assignment except for a specified unblinded statistician and programmer from the study contract research organization who will have access to the randomization code. The unblinded study personnel will not participate in study procedures or data analysis prior to unblinding of the study data to all study-related personnel upon database lock. If an interim analysis is conducted, then unblinded personnel who are not otherwise involved in the study will prepare the data for review.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 9, 2021
• Study Start: August 15, 2021
• Primary Completion: June 7, 2023
• Study Completion: June 8, 2023
• Last Updated: July 1, 2025
• Results First Posted: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (8); US (8)