Laryngopharyngeal RefluxPhase 2FLUTTERNCT04383262
Fosamprenavir for Laryngopharyngeal Upper Airway Tissue Treatment and Enzyme Reduction
A Phase 2 study testing Fosamprenavir Calcium in people with Laryngopharyngeal Reflux, run by Medical College of Wisconsin at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Laryngopharyngeal Reflux
- What is being tested?
- Fosamprenavir Calcium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 1 Oct 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
- 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:
- Hepatic Function Panel must be within normal limits
- Results from V1 safety labs must all be within normal limits
- Patient agrees not to make any changes to their usual diet and/or anti-reflux medications during the study.
- Patient is compliant with eDiary completion; that is, they have completed the eDiary questions on at least 5 days each week during the 14 calendar days before the start of the Treatment Period.
- 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 child-bearing potential not willing to comply with contraceptive requirements during the study treatment and for 1 week following the last dose of study drug.
- 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:
- Patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome) to any of the components of this product or to amprenavir.
- 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.
- History of human immunodeficiency virus (HIV) infection or positive for HIV 22. . Patients positive for hepatitis (Seropositive for hepatitis B surface antigen [HBsAg] or Hepatitis C 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.
- 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.
- Additionally, subjects without the following will be excluded:
- Ownership of an electronic with access to internet websites and email required to conduct the DRSD, PGI-S, and PGI-C
- Internet access
- A valid email address for notifications
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Froedtert Hospital
Milwaukee, Wisconsin, 53226
Ally Vandenberg, BSc, (414)955-2659, avandenberg@mcw.edu
Nikki Johnston, PhD, (414) 955-4075, njohnston@mcw.edu
About this study
Official title: A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy of Oral Fosamprenavir for Laryngopharyngeal Reflux
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.
Read the detailed description
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.
- Conditions
- Laryngopharyngeal Reflux
- Being tested
- Fosamprenavir Calcium, Placebo
- Medical subject headings
- Laryngopharyngeal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fosamprenavir CalciumDrug
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]).
PlaceboOther
Non-active placebo pill formulation
| Study group | Role | What they receive |
|---|---|---|
| Oral Fosamprenavir pills | Experimental | FOS: 1,400 mg fosamprenavir calcium b.i.d. (AM/PM) for 12 weeks Receives: Drug: Fosamprenavir Calcium |
| Placebo | Placebo comparator | Placebo pill for 12 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: Baseline to 12-week post-treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start1 Oct 2026 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Laryngopharyngeal RefluxStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Proof-of-Concept Efficacy Trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nikki Johnston, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04383262
- Sponsor's protocol ID
- PRO00056069
- Acronym
- FLUTTER
- Status last verified
- Sep 2026
- First submitted
- 1 May 2020
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy of Oral Fosamprenavir for Laryngopharyngeal Reflux
- ClinicalTrials.gov ID
- NCT04383262
- Acronym / sponsor ID
- FLUTTER / PRO00056069
- Conditions
- Laryngopharyngeal Reflux
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 12 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Proof-of-Concept Efficacy Trial
| Arm | Type | Receives |
|---|---|---|
| Oral Fosamprenavir pills | Experimental | Drug: Fosamprenavir CalciumFOS: 1,400 mg fosamprenavir calcium b.i.d. (AM/PM) for 12 weeks |
| Placebo | Placebo comparator | Other: PlaceboPlacebo pill for 12 weeks. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fosamprenavir CalciumA 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]). | Drug | Oral Fosamprenavir pills |
| PlaceboNon-active placebo pill formulation | Other | Placebo |
Primary outcome
Change in Reflux Symptom Index (RSI)
Time frame: Baseline to 12-week post-treatment.
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)
Change in Daily Symptom Reflux Diary (DRSD)
Time frame: Baseline to 12-week post-treatment.
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fosamprenavir Calcium in people with Laryngopharyngeal Reflux, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ally Vandenberg, BSc ((414)955-2659, avandenberg@mcw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Reflux Symptom Index (RSI) (time frame: Baseline to 12-week post-treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.