Clinical trial NCT02780752: A Study of Oral Hymecromone and Hyaluronan Synthesis
Official title: Dose Ranging Studies of Oral Hymecromone on Hyaluronan Synthesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Respiratory Disease
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2016-05-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in sputum hyaluronan concentration over the study period
timeFrame: From baseline to day 4
measure: Change in serum hyaluronan concentration over the study period
timeFrame: From baseline to day 4
measure: Change in serum hymecromone concentration over the study period
timeFrame: From baseline to day 4
Secondary outcomes:
measure: The safety and tolerability (as codified by Common Terminology Criteria for Adverse Events (CTCAE) v5.0) of oral hymecromone over the study period
timeFrame: Through study completion, an average of 11 days
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Paul Bollyky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.