Artesunate for Pulmonary Arterial Hypertension

((STOP-PAH) Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph C. Wu

Must be taking: PDE5 inhibitors, guanylate cyclase stimulators

Disqualifiers: Serious concomitant morbidity, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 20 weeks

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should already be on certain treatments for pulmonary arterial hypertension, so you might continue those.

How does the drug artesunate differ from other treatments for pulmonary arterial hypertension?

Artesunate is unique because it is originally an antimalarial drug that has shown potential benefits in heart conditions by activating specific protective pathways in the heart. This mechanism is different from standard treatments for pulmonary arterial hypertension, which typically focus on relaxing blood vessels or reducing blood pressure. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a 20-week, Phase 1, single-center, open-label, dose-escalation study evaluating the safety and tolerability of daily oral artesunate in patients with PAH.

Research Team

Roham Zamanian, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for patients with Pulmonary Arterial Hypertension (PAH). Specific eligibility criteria are not provided, but typically participants would need to have a confirmed diagnosis of PAH and be in stable condition to participate.

Inclusion Criteria

My heart and lung condition is stable even after taking various treatments.

Exclusion Criteria

Participants with serious concomitant morbidity per investigator assessment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral artesunate in a dose-escalation study

20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment during a washout period

4 weeks

Treatment Details

Interventions

• Artesunate

Trial Overview The study is testing the safety and how well people can tolerate different doses of an oral medication called Artesunate. It's a Phase 1 trial that lasts for 20 weeks at a single center where everyone knows what treatment they're getting.

Participant Groups

Group I: Open Label Treatment Arm Experimental Treatment 1 Intervention

Dose escalating study with a Follow-up (washout) Period: Total study period of the open-label study: 14 weeks Screening Period: up to 4 weeks Treatment Period (20 mg TID): 4 weeks Treatment Period (40 mg TID): 4 weeks Treatment Period (60 mg TID): 4 weeks Follow-up (washout) Period: 2 weeks after treatment period ends

Who Is Running the Clinical Trial?

Joseph C. Wu

Lead Sponsor

Trials

3

Recruited

40+

Findings from Research

Artesunate, an antimalarial drug, is rapidly converted to its active form, dihydroartemisinin, with peak levels of artesunate reached within 5 minutes and dihydroartemisinin within approximately 37.5 minutes after oral administration in rats.

The conversion and absorption of artesunate are influenced by the pH of the gastrointestinal tract, leading to faster absorption in the stomach compared to higher pH environments, which affects the drug's overall efficacy and action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of artesunate after single oral administration to rats. Olliaro, PL., Nair, NK., Sathasivam, K., et al.[2019]

In a randomized trial with 23 colorectal cancer patients, oral artesunate showed potential anti-cancer effects, with 67% of patients experiencing significant tumor cell apoptosis compared to 55% in the placebo group.

Artesunate was generally well tolerated, and during a median follow-up of 42 months, only 1 patient in the artesunate group experienced cancer recurrence compared to 6 in the placebo group, suggesting a possible benefit in preventing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. Krishna, S., Ganapathi, S., Ster, IC., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of artesunate after single oral administration to rats. [2019]

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

Artesunate inhibits the growth of gastric cancer cells through the mechanism of promoting oncosis both in vitro and in vivo. [2018]

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

The Antimalarial Drug Artesunate Attenuates Cardiac Injury in A Rodent Model of Myocardial Infarction. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Effects of artesunate on the invasion of lung adenocarcinoma A549 cells and expression of ICAM-1 and MMP-9]. [2021]