Fosamprenavir for Laryngopharyngeal Upper Airway Tissue Treatment and Enzyme Reduction

NCT04383262 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00056069
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Laryngopharyngeal Reflux (LPR) is a common condition that causes symptoms like chronic cough, throat clearing, hoarseness, and trouble swallowing. If not treated, LPR can lead to long-term throat damage and may increase the risk of throat cancer. More than 20% of the people in the United States are estimated to have LPR, yet there is no effective medication approved to treat it. Drugs called proton pump inhibitors (PPIs) are often used to treat LPR, even though they were designed for stomach acid problems. These medications reduce acid but do not stop reflux from happening, so they often do not help LPR patients. Despite poor results, PPIs are widely prescribed, are very costly, and can cause side effects. Research shows that a digestive enzyme called pepsin plays a key role in LPR. Pepsin can damage the throat and voice box even when acid is not present. Laboratory studies found that certain HIV medications can block damage caused by pepsin. People taking these medications for HIV appear to have a much lower rate of LPR. This study will test fosamprenavir, an FDA-approved HIV drug, as a treatment for LPR. We will conduct a 14-week, double-blind, placebo-controlled clinical trial in patients with LPR who did not improve with standard treatment. Participants will receive either fosamprenavir or placebo, randomly, and symptoms will be measured before and after treatment using standard questionnaires and daily symptom tracking. Because there is no effective medical treatment for LPR. this study aims to test a safe, existing drug that targets the underlying cause of the disease.

Conditions

Laryngopharyngeal Reflux

Outcome Measures

Primary Outcomes (2)

• Change in Reflux Symptom Index (RSI)

  The absolute change from baseline (i.e., Pretreatment) in symptom severity as indicated by RSI Score over time, with the primary treatment comparison at Week 12 (End of Treatment Visit)

  Baseline to 12-week post-treatment.

• Change in Daily Symptom Reflux Diary (DRSD)

  The absolute change from baseline (i.e., Pretreatment) in symptom severity as indicated by Weekly Total DRSD Score (WTDS) over time, with the primary treatment comparison at Week 12 (End of Treatment Visit)

  Baseline to 12-week post-treatment.

Other Outcomes (5)

• Change in Reflux Finding (RFS)

  Baseline to 12-week post-treatment.

• Change in Reflux Symptom Scale (RSS).

  Baseline to 12-week post-treatment.

• Change in Reflux Sign Assessment (RSA)

  Baseline to 12-week post-treatment.

Study Arms (2)

Oral Fosamprenavir pills

EXPERIMENTAL

FOS: 1,400 mg fosamprenavir calcium b.i.d. (AM/PM) for 12 weeks

Drug: Fosamprenavir Calcium

Placebo

PLACEBO COMPARATOR

Sodium Alginate: for 12 weeks.

Other: Placebo

Interventions

Fosamprenavir Calcium DRUG

A repurposing approach, prospective, placebo-controlled clinical trial of FOS-SA (used at 1,400 mg fosamprenavir calcium, twice daily) for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR (RSI \> 13, RFS \> 7 and MII-pH confirmed laryngeal reflux event\[s\]).

Oral Fosamprenavir pills

Placebo OTHER

Non-active placebo pill formulation

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• o Definition of women of child-bearing potential
• Non-post-menopausal female, who has not had a bilateral oophorectomy or medically documented ovarian failure. A subject may be considered to be post-menopausal when there is either:
• \- twelve (12) months of spontaneous amenorrhea or;
• \- six (6) months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL or;
• \- six (6) weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• A female who has had a tubal ligation sterilization or hysterectomy would not be considered to be of reproductive potential unless participating in activities of reproductive potential other than heterosexual intercourse (e.g., egg donation, participation in in vitro fertilization).
• Contraceptive requirements Fosamprenavir may decrease the effectiveness of combined hormonal contraception through significant CYP3A4 induction of estrogen. If subjects' preferred choice of contraception is combined hormonal contraception, subjects must also agree to use a second method of contraception (condom + spermicide) during study drug treatment.
• Other acceptable highly effective forms of contraception include:
• Medroxyprogesterone acetate injectable
• Intrauterine Device
• Female Sterilization
• Male Sterilization 4. Currently being treated with another investigational medical device and/or drug 5. A history of gastric or esophageal surgery 6. Gastrointestinal disease that might interfere symptom questionnaire, e.g. inflammatory bowel syndrome 7. A history of laryngeal or neck surgery including thyroidectomy and laryngomicroscopic surgery 8. Suspected esophageal cancer 9. Nasopharyngeal cancer 10. Previously undergone anti-reflux surgery 11. Polypharmacy (five or more concurrent medications due to comorbidities) 12. Any contraindications to FOS including the following:
• a. Patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome) to any of the components of this product or to amprenavir.
• b. Patients taking any drugs that are highly dependent on cytochrome P450 (CYP)3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Specifically i. Alpha 1-adrenoreceptor antagonist: Alfuzosin ii. Antimycobacterial: Rifampin iii. Antipsychotic: pimozide iv. Ergot derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine v. GI motility agent: Cisapride vi. Herbal product: St. John's wort ( Hypericum perforatum) vii. Lipid modifying agents: Lomitapide, lovastatin, simvastatin viii. Non-nucleoside reverse transcriptase inhibitor: Delavirdine ix. PDE5 inhibitor: Sildenafil (Revatio) x. Sedative/hypnotics: Midazolam, triazolam 13. Patients not willing to avoid eating grapefruit and Seville oranges for five days prior to the first day of dosing study drug through the final study visit.
• \. Patients taking any of the prohibited medications or foods listed in Section 5.6.3 15. Anticipated poor understanding or compliance of the study protocol 16. History of hepatic impairment 17. Sulfa Allergy 18. Hemophilia 19. Active tuberculosis (TB) or history of active TB. 20. History of latent TB (e.g., positive QuantiFERON-TB test) without history of active TB unless the subject has completed a documented course of prophylactic treatment.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Laryngopharyngeal Reflux

Interventions

fosamprenavir

Condition Hierarchy (Ancestors)

Gastroesophageal Reflux; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Laryngeal Diseases; Respiratory Tract Diseases

Central Study Contacts

Ally Vandenberg, BSc

CONTACT

(414)955-2659; avandenberg@mcw.edu

Nikki Johnston, PhD

CONTACT

(414) 955-4075; njohnston@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: We have partnered with Froedtert Hospital's Investigative Drug Services in order to randomize subjects to either treatment or placebo. Only FH IDS will have the key linking subjects to treatment groups, and the power to conduct an emergency unblinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Proof-of-Concept Efficacy Trial

Study Record Dates

• First Submitted: May 1, 2020
• First Posted: May 12, 2020
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)