A Phase 2 interventional study of Fosamprenavir Calcium and Placebo in Laryngopharyngeal Reflux, sponsored by Medical College of Wisconsin. Recruiting at 1 site in United States. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2026-09-10.
Sponsored by Medical College of Wisconsin · Phase 2, Interventional, and Treatment
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.
Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and if left untreated can promote the development of laryngeal cancer. More than 20% of the United Stated population suffer from LPR, yet there is no effective medical therapy. Proton pump inhibitors (PPIs), which inhibit gastric acid production but do not prevent reflux events, continue to be prescribed for LPR despite their poor efficacy for this patient population, high cost ($26 billion/year), and associated risks. Pepsin, detected in the airway of these patients and now known to cause laryngeal inflammation and promote disease independent of gastric acid, is a key therapeutic target. We report preclinical studies of select HIV inhibitors that bind to and inhibit pepsin and thus hold promise for the treatment of LPR. In support, a very low incidence of LPR was found in patients taking these drugs compared to the general population. HIV inhibitors are ideal drugs to repurpose because they target a foreign virus. Thus, a repurposing approach can be used to safely perform proof of concept testing of the efficacy of a pepsin inhibitor for LPR.
The objective of this study is to evaluate the efficacy and safety of fosamprenavir (FOS), administered orally for improving symptoms of laryngopharyngeal reflux (LPR). The Specific Aim of this project is to perform a 12-week randomized, double-blind, placebo-controlled clinical trial to assess the efficacy of fosamprenavir pills for LPR. Fosamprenavir will be used at the FDA approved, manufacturers recommended dose for HIV for 12 weeks in medically refractory patients with clinically diagnosed moderate/severe LPR and combined multi-channel intraluminal impedance - pH (MII-pH) confirmed laryngeal reflux events. Routine clinical outcome measures for LPR (Reflux Symptom Index, Reflux Finding Score, Voice Handicap Index) will be documented pre- and post-treatment with Oral Fosamprenavir for LPR (n = 52) and placebo (n = 52). Additional research measures will include repeat administration of a newly created Daily Symptom Reflex Diary, as well as an intermittently distributed Patient Global Impression - Static \& Change scales.
Participants for this study will be recruited from the Department of Otolaryngology (ENT) at Froedtert Hospital in Milwaukee, Wisconsin. Patients seen by Froedtert ENT laryngologists who receive a diagnosis of laryngopharyngeal reflux (LPR) during a standard-of-care visit will be informed about the study and offered additional information regarding participation. Individuals interested in participating will be invited to attend a separate screening and consent visit at the Adult Translational Research Unit (ATRU) on campus. The study consists of eight research visits, including the screening/consent visit, conducted over approximately 14 weeks. Up to two study visits may be completed remotely (Visit 2 and Visit 8).
Data will be collected from participant medical charts for the 3 standard-of-care clinic visits; Clinic visit 1 \& 2 are for diagnosis of LPR, while clinic visit 3 is a follow-up that occurs 14 weeks after visit 1 \& 2.
56 studies on the registry are indexed under Laryngopharyngeal Reflux; 8 are open to participants now.
This study's planned enrollment of 104 is above the median of 72 across 41 interventional studies indexed under Laryngopharyngeal Reflux.
Browse Laryngopharyngeal Reflux studies →Medical College of Wisconsin is the lead sponsor of 548 studies on the registry; 122 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 57 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
1. Clinical diagnosis of LPR 2. Age ≥ 18 years 3. RSI > 13 4. RFS > 7 5. Documented LPR by MII-pH testing (> 1 proximal event) 6. Failed 3 month bid PPI therapy 7. Attending laryngology clinic with study providers, and having flexible laryngoscopy and MII-pH testing per routine clinical care with a minimum of three months between clinic visits (standard practice) 8. For continued participation after ATRU V1/V2:
Patient is compliant with continuing any current PPI (if using) during the 14 calendar days before the start of the Treatment Period. Patients are considered compliant if, as reported in the daily eDiary, they continued taking their current PPI (if using) on at least 5 days each week during the 14 calendar days before the start of the Treatment Period.
4.2 EXCLUSION CRITERIA 1. Age ≥ 65 years 2. Patient is not fluent and literate in English. 3. Pregnant (or plan to be) and nursing mothers 4. Women of not willing to comply with requirements during the study treatment and for 1 week following the last dose of study drug.
o Definition of women of child-bearing potential
Non- 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 unless participating in activities of reproductive potential other than heterosexual intercourse (e.g., egg donation, participation in in vitro fertilization).
Other acceptable highly effective forms of contraception include:
a. Patients with previously demonstrated (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.
14. 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.
21. History of (HIV) infection or positive for HIV 22. . Patients positive for hepatitis (Seropositive for surface antigen [HBsAg] or virus [HCV] RNA positive) or taking HCV protease inhibitors such as boceprevir, simeprevir and paritaprevir 23. Not willing to refrain from taking biotin containing supplement for at least 12 hours before Visit 1.
24. Patient has an acute or chronic condition that, in the Investigator's opinion, would limit the patient's ability to complete or participate in this clinical study.
25. Additionally, subjects without the following will be excluded:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FOS: 1,400 mg fosamprenavir calcium b.i.d. (AM/PM) for 12 weeks
Drug: Fosamprenavir Calcium
Placebo pill for 12 weeks.
Other: Placebo
A repurposing approach, prospective, placebo-controlled clinical trial of Fosamprenavir (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\[s\]).
Non-active placebo pill formulation
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)
Time frame: 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)
Time frame: Baseline to 12-week post-treatment.
Change in Reflux Finding (RFS)
The absolute change from baseline in endoscopic signs severity as indicated by Reflux Finding Score (RFS) over time, with the primary treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment.
Change in Reflux Symptom Scale (RSS).
The absolute change from baseline in symptom severity as indicated by Reflux Symptom Score (RSS) over time, with the primary treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment.
Change in Reflux Sign Assessment (RSA)
The absolute change from baseline in endoscopic signs severity as indicated by Reflux Sign Assessment (RSA) score over time, with the primary treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment.
Change in Voice Handicap Index 10 (VHI-10)
The absolute change from baseline in symptom severity as indicated by Voice Handicap Index-10 (VHI-10) score over time, with the primary treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment.
Change in symptom-free days
The absolute change from baseline in weekly overall reflux symptom-free days as indicated by Weekly Symptom-Free Days (WSFD; i.e. the total number of symptom-free days per week, with symptom-free defined as "Did not have" response for all items on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to week 12
Change in "throat-clearing"
The absolute change from baseline in weekly "throat-clearing" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "throat-clearing" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "sensation of something stuck in the throat"
The absolute change from baseline in weekly "sensation of something stuck in the throat" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "sensation of something stuck in the throat" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "excess mucus in the throat"
The absolute change from baseline in weekly "excess mucus in the throat" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "excess mucus in the throat" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "throat pain"
The absolute change from baseline in weekly "throat pain" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "throat pain" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "problem with the sound of your voice"
The absolute change from baseline in weekly "problem with the sound of your voice" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "problem with the sound of your voice" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "difficulty swallowing"
The absolute change from baseline in weekly "difficulty swallowing" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "difficulty swallowing" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "heartburn"
The absolute change from baseline in weekly "heartburn" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "heartburn (sensation of burning feeling behind the breastbone)" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "regurgitation"
The absolute change from baseline in weekly "regurgitation" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "regurgitation (liquid or food moving upwards towards your throat or mouth)" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "abdominal pain"
The absolute change from baseline in weekly "abdominal pain" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "abdominal pain" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "bad breath"
The absolute change from baseline in weekly "bad breath" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "bad breath" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "cough"
The absolute change from baseline in weekly "cough" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "cough" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in "difficulty breathing"
The absolute change from baseline in weekly "difficulty breathing" symptom-free days (i.e. the total number of days per week that the patient responded "Did not have" for "difficulty breathing" item on the DRSD), over time, with the primary exploratory treatment comparison at Week 12
Time frame: Baseline to 12-week post-treatment
Change in Reflux Symptom Index (RSI) up to week 4
The absolute change from baseline in symptom severity as indicated by RSI score over time, (up to Week 4), with the primary treatment comparison at Week 4
Time frame: Baseline to week 4 post-treatment.
Change in Reflux Symptom Index (RSI) up to week 8
The absolute change from baseline in symptom severity as indicated by RSI score over time, (up to Week 8), with the primary treatment comparison at Week 8
Time frame: Basaeline to week 8
Change in Reflux Symptom Score (RSS) up to week 4
The absolute change from baseline in symptom severity as indicated by RSS score over time, (up to Week 4), with the primary treatment comparison at Week 4
Time frame: Baseline to week 4
Change in Reflux Symptom Score (RSS) up to week 8
The absolute change from baseline in symptom severity as indicated by RSS score over time, (up to Week 8), with the primary treatment comparison at Week 8
Time frame: Baseline to week 8
Responders by Reflux Symptom Index (RSI)
Proportion of patients who are Responders (by RSI) at Week 12
Time frame: Baseline to week 12
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Jul 2027, 9 months later.
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Studies of the drug tested here: Fosamprenavir
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