Vonoprazan Formulations in Healthy Participants

Overseen By Phathom Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Phathom Pharmaceuticals, Inc.

Must not be taking: CYP3A4 inducers

Disqualifiers: Hepatitis, HIV, Neurological, Gastrointestinal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 periods with 5-day washouts

25 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking any prescription and over-the-counter medications (except hormonal birth control and acetaminophen up to 2 g per day) at least 14 days before the first dose of the study drug and throughout the study.

What data supports the effectiveness of the drug vonoprazan?

Research shows that vonoprazan is effective in treating acid-related conditions, such as non-erosive reflux disease and preventing ulcers caused by NSAID use. It has been found to be as effective as lansoprazole, another acid-reducing drug, in healing erosive esophagitis and treating gastric or duodenal ulcers. ^{1 2 3 4 5}

Is vonoprazan generally safe for humans?

Vonoprazan has been studied for safety in healthy individuals and patients with acid-related conditions. Research shows it is generally well-tolerated, with studies evaluating its safety over both short and long-term use. ^{1 3 4 6 7}

How is the drug vonoprazan different from other treatments for acid-related conditions?

Vonoprazan is unique because it is a potassium-competitive acid blocker, which works differently from traditional proton pump inhibitors (PPIs) by blocking acid production in the stomach more effectively and quickly. This novel mechanism may offer better healing for conditions like erosive esophagitis and ulcers compared to existing treatments. ^{1 3 4 5 8}

What is the purpose of this trial?

The primary objective of this study is to assess the bioavailability (BA) of a single oral dose of two vonoprazan orally disintegrating tablet formulations (ODT-1 or ODT-2) administered without water or mixed with water and administered via a syringe relative to the vonoprazan tablet in healthy participants.

Research Team

Medical Director

Principal Investigator

Phathom Pharmaceuticals

Eligibility Criteria

This trial is for healthy individuals who can take a single dose of the study drug. Specific eligibility criteria are not provided, but typically participants must be adults without any significant medical conditions.

Inclusion Criteria

Participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at Screening

Participant agrees to comply with all protocol requirements

I am not pregnant, as confirmed by tests.

Exclusion Criteria

I have not donated blood in the last 30 days.

Participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at Screening

I have a serious health condition that could affect my trial participation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of vonoprazan in different formulations across 5 periods with a minimum 5-day washout interval between doses

5 periods with 5-day washouts

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Vonoprazan

Trial Overview The study is testing two different formulations of Vonoprazan orally disintegrating tablets (ODT-1 and ODT-2), taken with or without water, compared to the standard Vonoprazan tablet. The goal is to see how well each method works in healthy people.

Participant Groups

Group I: Sequence E, A, D, B, C: Vonoprazan 10 mg Experimental Treatment 3 Interventions

Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio. On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to: * Treatment A: Vonoprazan 10 mg ODT-1 without water * Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe * Treatment C: Vonoprazan 10 mg ODT-2 without water * Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe * Treatment E (reference): Vonoprazan 10 mg tablet. There will be a washout interval of a minimum of 5 days between study drug dosing in each period.

Group II: Sequence D, C, A, E, B: Vonoprazan 10 mg Experimental Treatment 3 Interventions

Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio. On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to: * Treatment A: Vonoprazan 10 mg ODT-1 without water * Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe * Treatment C: Vonoprazan 10 mg ODT-2 without water * Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe * Treatment E (reference): Vonoprazan 10 mg tablet. There will be a washout interval of a minimum of 5 days between study drug dosing in each period.

Group III: Sequence C, E, B, A, D: Vonoprazan 10 mg Experimental Treatment 3 Interventions

Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio. On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to: * Treatment A: Vonoprazan 10 mg ODT-1 without water * Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe * Treatment C: Vonoprazan 10 mg ODT-2 without water * Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe * Treatment E (reference): Vonoprazan 10 mg tablet. There will be a washout interval of a minimum of 5 days between study drug dosing in each period.

Group IV: Sequence B, D, E, C, A: Vonoprazan 10 mg Experimental Treatment 3 Interventions

Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio. On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to: * Treatment A: Vonoprazan 10 mg ODT-1 without water * Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe * Treatment C: Vonoprazan 10 mg ODT-2 without water * Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe * Treatment E (reference): Vonoprazan 10 mg tablet. There will be a washout interval of a minimum of 5 days between study drug dosing in each period.

Group V: Sequence A, B, C, D, E: Vonoprazan 10 mg Experimental Treatment 3 Interventions

Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio. On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to: * Treatment A: Vonoprazan 10 mg ODT-1 without water * Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe * Treatment C: Vonoprazan 10 mg ODT-2 without water * Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe * Treatment E (reference): Vonoprazan 10 mg tablet. There will be a washout interval of a minimum of 5 days between study drug dosing in each period.

Who Is Running the Clinical Trial?

Phathom Pharmaceuticals, Inc.

Lead Sponsor

Trials

14

Recruited

4,400+

Findings from Research

On-demand therapy using 20-mg vonoprazan for 8 weeks in 30 patients with non-erosive reflux disease showed similar effectiveness to continuous proton pump inhibitor (PPI) maintenance therapy, as patient satisfaction and symptom scores remained unchanged.

The study found that patients took a median of 11 tablets during the 8-week period, with 30% using vonoprazan regularly, indicating that on-demand therapy can be a practical alternative for managing reflux symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease. Hoshikawa, Y., Kawami, N., Hoshino, S., et al.[2020]

Vonoprazan (10 mg and 20 mg) was found to be non-inferior to lansoprazole (15 mg) in preventing recurrent peptic ulcers in patients taking long-term NSAIDs, with recurrence rates of 3.3% and 3.4% for vonoprazan compared to 5.5% for lansoprazole over 24 weeks.

The study, which included 642 outpatients and lasted over 1 year, showed that vonoprazan was effective and well tolerated, with a safety profile similar to that of lansoprazole, indicating it is a safe option for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study. Mizokami, Y., Oda, K., Funao, N., et al.[2018]

TAK-438 (vonoprazan) demonstrated rapid absorption and effective gastric acid suppression in healthy male subjects, achieving over 90% intragastric pH ≥4 for 24 hours at a 40 mg dose, indicating its strong efficacy as an acid blocker.

The drug was well tolerated across all doses, with no serious adverse events reported, suggesting it could be a safe alternative to traditional proton pump inhibitors for treating acid-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects. Sakurai, Y., Nishimura, A., Kennedy, G., et al.[2022]

In a study of 409 patients with erosive esophagitis, vonoprazan demonstrated non-inferiority to lansoprazole, with a higher healing rate of 99.0% compared to 95.5% for lansoprazole after 8 weeks, indicating its effectiveness in treating this condition.

During a long-term maintenance phase of 52 weeks, vonoprazan showed a low recurrence rate of erosive esophagitis (<10%) and was well-tolerated, suggesting it is a safe option for ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Ashida, K., Sakurai, Y., Hori, T., et al.[2022]

Vonoprazan (20 mg) demonstrated non-inferiority to lansoprazole (30 mg) in healing gastric ulcers, with 93.5% of patients achieving healing compared to 93.8% for lansoprazole, confirming its efficacy in this regard.

For duodenal ulcers, while 95.5% of vonoprazan-treated patients healed, it did not meet the non-inferiority criteria compared to lansoprazole (98.3%), indicating that while effective, it may not be as reliable for DU healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials. Miwa, H., Uedo, N., Watari, J., et al.[2020]

In a 12-month study involving 1268 patients in Japan, vonoprazan was found to be effective in preventing the recurrence of gastric and duodenal ulcers in patients taking long-term NSAIDs, with a low recurrence rate of 1.04%.

The safety profile of vonoprazan was favorable, with a very low incidence of adverse drug reactions (0.71%), indicating no new safety concerns for its use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and effectiveness of vonoprazan for prevention of gastric and duodenal ulcer recurrence in patients on nonsteroidal anti-inflammatory drugs in Japan: a 12-month post-marketing surveillance study. Kawai, T., Suzuki, C., Honda, Y., et al.[2023]

In a phase 3 study involving 476 Japanese patients with nonerosive reflux disease, vonoprazan 10 mg showed a significantly higher cumulative improvement rate for heartburn symptoms compared to placebo, indicating its potential efficacy in treating this condition.

While vonoprazan did not significantly increase the proportion of days without heartburn in the overall analysis, it did show a greater rate of complete heartburn resolution by the fourth week of treatment, and it was well tolerated with similar rates of mild adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Vonoprazan in Patients With Nonerosive Gastroesophageal Reflux Disease: A Randomized, Placebo-Controlled, Phase 3 Study. Kinoshita, Y., Sakurai, Y., Takabayashi, N., et al.[2023]

Using a physiologically relevant bicarbonate buffer (BCB) for testing enteric coated pantoprazole formulations revealed performance differences that standard pharmacopeial tests did not detect, highlighting the importance of using more relevant conditions for accurate evaluation.

The study suggests that incorporating BCB in the testing process can improve the predictability of in vitro-in vivo relationships (IVIVR) and potentially reduce risks in the development of generic formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically relevant dissolution conditions towards improved in vitro - in vivo relationship - A case study with enteric coated pantoprazole tablets. Amaral Silva, D., Gomes Davanço, M., Davies, NM., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety and effectiveness of vonoprazan for prevention of gastric and duodenal ulcer recurrence in patients on nonsteroidal anti-inflammatory drugs in Japan: a 12-month post-marketing surveillance study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Vonoprazan in Patients With Nonerosive Gastroesophageal Reflux Disease: A Randomized, Placebo-Controlled, Phase 3 Study. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Physiologically relevant dissolution conditions towards improved in vitro - in vivo relationship - A case study with enteric coated pantoprazole tablets. [2021]