Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF

(HFpEF Trial)

Recruiting at 14 trial locations

Overseen By Janice Durden

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Rivus Pharmaceuticals, Inc.

Must not be taking: GLP-1 antagonists, SGLT2 inhibitors

Disqualifiers: Malignancy, Bariatric surgery, Myocarditis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 134 days

67 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants have stable doses of their current medications for at least 30 days before screening, meaning no new medications or significant changes in dosage. If you are on diuretics, you must be on a stable regimen that allows for flexible dosing.

What safety data exists for the treatment evaluated under names like HU6, Placebo, Control, and Dummy Treatment?

The safety reporting in clinical trials is often inadequate, with only a small percentage of trials providing detailed information on adverse effects and reasons for withdrawal due to toxicity. Placebos, often used in trials, are not always harmless as their contents are not always inert, which can affect safety data interpretation. ^{1 2 3 4 5}

What makes the drug HU6 unique compared to other treatments?

The drug HU6 is unique because it is a synthetic cannabinoid that acts as a non-competitive NMDA receptor blocker, providing pain relief without the psychotropic effects typically associated with cannabinoids. This mechanism of action, combined with its ability to scavenge free radicals, makes it distinct from other treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests a new drug called HU6 by giving participants increasing doses to find the safest and most effective amount. It involves individuals who meet specific health criteria.

Research Team

Shaharyar Khan, PhD

Principal Investigator

Rivus Pharmaceuticals, Inc.

Eligibility Criteria

Inclusion Criteria

Adult male or female, ≥40 years of age.

Competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and must sign the form prior to the initiation of any study procedures.

You have to meet at least one of the following criteria for heart failure:

Exclusion Criteria

You have a currently active autoimmune disease affecting your connective tissues.

You have a specific type of heart condition called primary cardiomyopathy as determined by the doctor.

You have a current case of heart inflammation, either caused by COVID or another reason.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

40 days

1-2 visits (in-person)

Treatment

Participants receive HU6 or placebo in a dose escalation manner: 150 mg daily for 20 days, followed by 300 mg daily for 20 days, and 450 mg daily for 94 days if safety and tolerability are demonstrated.

134 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• HU6
• Placebo

Participant Groups

Group I: Active Treatment: HU6 Planned doses of HU6; N = 31 Experimental Treatment 1 Intervention

Group II: Placebo Comparator Non-active study drug N = 31 Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Rivus Pharmaceuticals, Inc.

Lead Sponsor

Trials

9

Recruited

540+

Findings from Research

A review of 192 randomized clinical trials revealed that safety information is often underreported, with only 46% specifying reasons for withdrawals due to toxicity and only 39% adequately reporting clinical adverse effects.

To enhance safety reporting, the study emphasizes the need for standardized scales for adverse effects, systematic data collection, and detailed reporting of severe reactions, suggesting that improved practices could lead to better safety insights in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving safety reporting from randomised trials. Ioannidis, JP., Lau, J.[2018]

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

In a review of 113 placebo-controlled randomized clinical trials published in 2016, only 19.5% of journal articles and 45.1% of study protocols provided descriptions of placebo contents, highlighting a significant lack of transparency in clinical trial reporting.

None of the journal publications explained the rationale for the choice of placebo ingredients, which raises concerns about the potential effects of active placebos on trial outcomes and complicates the assessment of the safety and efficacy of experimental interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals. Hong, K., Rowhani-Farid, A., Doshi, P.[2023]

In a randomized, double-blind clinical trial involving 125 patients with referred shoulder pain, applying a force to the C5 vertebra using a mechanically assisted instrument (MAI) significantly improved internal rotation strength after 6 months (P = 0.04).

While the treatment cohort experienced a reduction in the frequency of extreme shoulder pain (from weekly to monthly), there was no significant change in the severity of pain or other functional outcomes compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Applying a Force to C5 by a Mechanically Assisted Instrument on Referred Pain to the Shoulder. Hardas, GM., Murrell, GAC.[2021]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Improving safety reporting from randomised trials. [2018]

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

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals. [2023]

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

Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Applying a Force to C5 by a Mechanically Assisted Instrument on Referred Pain to the Shoulder. [2021]

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

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. [2020]

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

Suppression of neuropathic pain behavior in rats by a non-psychotropic synthetic cannabinoid with NMDA receptor-blocking properties. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance development. [2022]

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

Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist. [2019]

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

Cannabimimetic activity in rats and pigeons of HU 210, a potent antiemetic drug. [2019]

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

Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid. [2016]