A Study of Oral Hymecromone and Hyaluronan Synthesis

NCT02780752 | Completed Phase 1 FDA Drug

• 1 other identifier: IRB-43805
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to add further understanding to the doses of hymecromone that effectively and safely lead to the inhibition of hyaluronan synthesis. In this study we will investigate both circulating hyaluronan in the serum, as well as tissue hyaluronan, using sputum samples as a non-invasive surrogate. This is a parallel, open-label, single-center, dose-response study of hymecromone in healthy adults 18 years of age or older. Up to 18 participants will be enrolled. Participants will be treated for 4 days with study drug. Safety as well as biomarkers of pharmacokinetic and pharmacodynamic response will be monitored during therapy.

Conditions

Healthy; Respiratory Disease

Outcome Measures

Primary Outcomes (3)

• Change in sputum hyaluronan concentration over the study period

  From baseline to day 4

• Change in serum hyaluronan concentration over the study period

  From baseline to day 4

• Change in serum hymecromone concentration over the study period

  From baseline to day 4

Secondary Outcomes (1)

• The safety and tolerability (as codified by Common Terminology Criteria for Adverse Events (CTCAE) v5.0) of oral hymecromone over the study period

  Through study completion, an average of 11 days

Study Arms (3)

Oral hymecromone 400mg po three times per day

ACTIVE COMPARATOR

Participants will be administered oral hymecromone 400mg po three times per day (1200 mg)

Drug: hymecromone

Oral hymecromone 800 mg po three times per day (2400 mg)

ACTIVE COMPARATOR

Participants will be be administered oral hymecromone 800 mg po three times per day (2400 mg)

Drug: hymecromone

Oral hymecromone 1200 mg three times per day (3600 mg)

ACTIVE COMPARATOR

Participants will be administered oral hymecromone 1200 mg three times per day (3600 mg)

Drug: hymecromone

Interventions

hymecromone DRUG

Oral Hymecromone

Also known as: 4-Methylumbelliferone

Oral hymecromone 1200 mg three times per day (3600 mg); Oral hymecromone 400mg po three times per day; Oral hymecromone 800 mg po three times per day (2400 mg)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 18-65 years of age
• Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on history, physical exam
• BMI between 18.5 - 30 kg/m2
• Taking no medications for at least 1 week before and during study enrollment, including drugs of abuse, prescription or OTC medications
• Male subjects who are heterosexually active must use an acceptable method of contraception (abstinence, condom with or without spermicidal agent, or partner contraceptive use as described in requirements for female subjects) to avoid pregnancy in their partner for the entire study period
• Female subjects who are heterosexually active must use an acceptable method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or Hormone-based contraceptive
• Be able to provide written informed consent and comply with requirements of the study
• Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 3pm the night before a study day until completion of that study day
• Be able to read, speak and understand English
• Able and willing to understand the study, adhere to all study procedures, and provide written informed consent

You may not qualify if:

• Subjects with a history of gastrointestinal disease including gastroesophageal reflux disease, gastritis, peptic ulcer disease or dyspepsia
• Subjects with history of dysphagia, achalasia, or difficulty swallowing capsules, tablets or pills
• Subjects with liver failure or LFTs above the upper limit of normal
• Subjects with clinically significant elevations in SCr, BUN or other screening laboratory tests as determined by study physician
• Subjects with a baseline corrected Fridericia's QT interval (QTcF) \>450ms and a baseline ECG abnormalities which in the opinion of the study physician, is clinically significant
• Subjects with ongoing alcohol or illegal drug use
• Subjects who are pregnant, lactating or attempting to conceive
• Known allergy to hymecromone or any component thereof
• Physician concern that participant may not adhere to the study protocol
• Current participation in another clinical trial

Sponsors & Collaborators

• Paul Bollyky: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

Related Publications (2)

• Salman L, Martinez L, Faddoul G, Manning C, Ali K, Salman M, Vazquez-Padron R. Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next? Kidney360. 2023 Jun 1;4(6):e851-e860. doi: 10.34067/KID.0000000000000126. Epub 2023 Apr 14.

  PMID: 37055910 DERIVED

• Rosser JI, Nagy N, Goel R, Kaber G, Demirdjian S, Saxena J, Bollyky JB, Frymoyer AR, Pacheco-Navarro AE, Burgener EB, Rajadas J, Wang Z, Arbach O, Dunn CE, Kalinowski A, Milla CE, Bollyky PL. Oral hymecromone decreases hyaluronan in human study participants. J Clin Invest. 2022 May 2;132(9):e157983. doi: 10.1172/JCI157983.

  PMID: 35499083 DERIVED

MeSH Terms

Conditions

Respiration Disorders

Interventions

Hymecromone

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Umbelliferones; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Paul Bollyky, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Participants will be assigned to one of three treatment groups, each including up to 6 participants, with treatment over 4 days of different doses of oral hymecromone. Following a wash-out period, participants are allowed to re-enroll into different treatment groups to provide intra-patient dose comparisons.

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: May 23, 2016
• Study Start: December 1, 2020
• Primary Completion: May 10, 2021
• Study Completion: May 10, 2021
• Last Updated: June 16, 2021

Record last verified: 2021-06

Locations

US (1)