BIO 300 Oral Suspension for Healthy Volunteers

Overseen By Vice President of Research and Development

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Humanetics Corporation

Must not be taking: Prescription medications

Disqualifiers: Arrhythmia, QTc prolongation, Hepatitis, others

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

Compensation: Varies

Number of Visits: 16

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a two-part study of BIO 300 Oral Suspension in healthy male and female volunteers. The first part is a multiple ascending dose (MAD) study to test the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the drug when given as daily doses over 14 days. The study will enroll three cohorts each receiving a different daily dose: 2000 mg, 3000 mg, or 4000 mg. A fourth group may be added depending on results on the first three cohorts. Each cohort will include 10 participants (5 men, 5 women), with at least 8 completing all study steps. Participants will follow a special diet low in soy-based foods and will fast before certain doses. Blood samples and health checks will be done throughout the study to assess safety, drug is absorption and distribution in the body (PK), and its effects (PD). Safety will be reviewed after each group finishes to decide if the next dose level is safe to proceed. The second part of the study is a food effect study to examine how food effects the PK of a single dose of BIO 300 Oral Suspension. This study will enroll 16 participants (8 men, 8 women) and will be split into two groups: one group will take the drug after fasting for 10 hours and the other will take the drug after eating a high-fat meal. After a 7-day break, participants will switch conditions (the previously fasted group will take the drug with food, and the previously fed group will take the drug after fasting). Blood samples and health checks will measure how food influences drug absorption (PK) and safety. Both the MAD study and food effect study aim to ensure the drug is safe and provide data on how it behaves in the body under different conditions.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription or over-the-counter medications, including dietary and herbal supplements, for 7 days before the study starts and during the study. However, acetaminophen and ibuprofen are allowed in limited amounts at the discretion of the Investigator.

What safety data exists for BIO 300 Oral Suspension in humans?

The available research does not specifically mention BIO 300 Oral Suspension, but studies on drug safety in healthy volunteers show that adverse effects are generally rare and minor. In a survey, minor adverse effects were reported in about 6.9% of cases, with no lasting harm. ^{1 2 3 4 5}

How does the drug BIO 300 Oral Suspension differ from other treatments?

BIO 300 Oral Suspension is unique because it is designed as an oral suspension, which may improve the ease of ingestion and potentially enhance the bioavailability (how well a drug is absorbed in the body) of its active ingredients compared to traditional tablet forms. This could make it more effective or easier to take for some patients. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for healthy men and women who can follow a special diet low in soy-based foods. Participants must be willing to fast before doses and commit to the study schedule, including blood samples and health checks. Those with allergies or conditions affecting drug absorption are likely excluded.

Inclusion Criteria

BMI 18-30 kg/m2

No clinically significant abnormalities identified by medical history, physical examination, vital signs, ECG, and clinical laboratory tests in the opinion of the Investigator

I have taken a pregnancy test within the last 3 days and it was negative.

Exclusion Criteria

I tested positive for Hep B, Hep C, or HIV but my Hep C follow-up test was negative.

Clinically significant immunodeficiency disorder in the opinion of the Investigator

Participants recruited for the food effect study that cannot consume the entire standardized high fat meal without substitutions

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple Ascending Dose (MAD) Study

Participants receive ascending doses of BIO 300 Oral Suspension daily for 14 days to assess safety, PK, and PD.

14 days

Daily visits for 14 days, with additional visits on days 15, 16, and 21

Food Effect Study

Participants receive a single dose of BIO 300 Oral Suspension under fed and fasted conditions to assess the effect of food on PK.

Approximately 2 weeks including washout period

Visits on dosing days and follow-up on days 2 and 3 after each dose

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 days after the last dose

Treatment Details

Interventions

• BIO 300 Oral Suspension

Trial Overview The trial tests BIO 300 Oral Suspension's safety and how it's processed by the body (PK/PD) over daily doses for two weeks at varying strengths (2000 mg, 3000 mg, or possibly up to 4000 mg). It also examines how food affects the drug's absorption with participants trying both fasting and fed conditions.

Participant Groups

Group I: Multiple Ascending Dose Experimental Treatment 1 Intervention

The multiple ascending dose study has a single arm. Three cohorts are enrolled sequentially and given ascending doses of study intervention.

Group II: Food Effect: Fed-Fasted Arm Experimental Treatment 1 Intervention

Food effect study arm that is administered the study intervention first under fed conditions and then under fasted conditions following crossover.

Group III: Food Effect: Fasted-Fed Experimental Treatment 1 Intervention

Food effect study arm that is administered the study intervention first under fasted conditions and then under fed conditions following crossover.

Who Is Running the Clinical Trial?

Humanetics Corporation

Lead Sponsor

Trials

8

Recruited

300+

Findings from Research

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

Live Biotherapeutic Products (LBPs) have therapeutic potential by interacting with the microbiota and modulating host-microbiota relationships, but they face significant challenges in obtaining marketing authorization in the EU due to their unique safety assessment requirements.

A proposed roadmap for risk analysis and development programs is essential for LBPs, focusing on their specific characteristics and interactions with patients to ensure safety in non-clinical and early clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Live Biotherapeutic Products, A Road Map for Safety Assessment. Rouanet, A., Bolca, S., Bru, A., et al.[2023]

Biosimilars, while similar in efficacy to reference drugs, may have different safety profiles, particularly concerning adverse reactions, necessitating ongoing monitoring after approval.

The European Medicines Agency requires biosimilar applicants to submit a risk management plan and pharmacovigilance program to address potential safety issues, especially immunogenicity, throughout the drug's lifecycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biosimilars: pharmacovigilance and risk management. Zuñiga, L., Calvo, B.[2013]

In a survey of 459 members of the British Pharmacological Society, it was found that drugs were administered to 8163 healthy volunteers, with only 6.9% experiencing minor adverse effects and 0.04% facing potentially life-threatening effects, indicating a very low risk associated with these studies.

Among 7607 healthy student volunteers, only 6.0% reported minor adverse effects during drug administration for educational purposes, with no severe adverse effects noted, reinforcing the overall safety of drug administration in healthy volunteer studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healthy volunteer studies in Great Britain: the results of a survey into 12 months activity in this field. Orme, M., Harry, J., Routledge, P., et al.[2019]

The EU council directives provide a comprehensive regulatory framework to ensure the safety of biotechnological medicinal products, focusing on benefit/risk evaluation and quality assessment.

The framework emphasizes the importance of preclinical safety and efficacy testing before new drug applications are approved, ensuring that new treatments are both safe and effective for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of biotechnological products. Bass, R., Purves, J., Amati, MP.[2019]

Oral bioavailability is crucial for understanding how food bioactive ingredients can provide health benefits, and factors like bioaccessibility and absorption significantly limit this process.

In vitro studies on oral bioavailability help food and drug manufacturers create better delivery systems and determine appropriate dosages of bioactive compounds to enhance health benefits while minimizing toxicity risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability and bioaccessibility of food bioactive compounds; overview and assessment by in vitro methods. Dima, C., Assadpour, E., Dima, S., et al.[2021]

The study suggests that the AUC/dose ratio can predict the risk of bioinequivalence for oral drug products, indicating that this parameter is crucial for assessing the safety and efficacy of generic medications.

Data from six Japanese pharmaceutical companies showed that bioequivalence studies for BCS class 1 and class 3 drugs require a consistent number of subjects, supporting the idea that biowaivers could be appropriate for these drug classes, thus potentially streamlining the approval process for generic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A perspective for biowaivers of human bioequivalence studies on the basis of the combination of the ratio of AUC to the dose and the biopharmaceutics classification system. Sakuma, S., Tachiki, H., Uchiyama, H., et al.[2011]

In a study of 133 approved generic formulations of BCS Class III drugs, only 30.08% met the stringent formulation criteria for qualitative (Q1) sameness and quantitative (Q2) similarity, yet all formulations demonstrated bioequivalence in terms of absorption parameters (AUC and Cmax).

The results suggest that the absorption of BCS Class III drugs is more influenced by their biopharmaceutic and physicochemical properties rather than the specific formulations or excipients used, indicating potential flexibility in formulation design for generic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the Similarity of Formulations and Excipients of Approved Generic Drug Products on In Vivo Bioequivalence for Putative Biopharmaceutics Classification System Class III Drugs. Ren, P., Chan, T., Yang, WC., et al.[2023]

The paper by Ono and Sugano suggests that biowaivers based on the Biopharmaceutics Classification System (BCS) could be used to evaluate the bioequivalence of orally disintegrating tablets (ODTs) compared to immediate release formulations for Class III drugs.

However, there are concerns that this approach has not been adequately tested with products that have different bioavailabilities, and it may overlook important factors such as the common way ODTs are taken (without water), which could affect gastric emptying and thus bioavailability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the BCS biowaivers of orally disintegrating tablets. García-Arieta, A., Gordon, J.[2017]

The study demonstrated that a new powder for oral suspension of lapatinib is bioequivalent to the standard 250-mg tablets, allowing for easier ingestion for patients with advanced cancer, with 144 participants involved in the trial.

No unexpected safety issues were reported, and the absorption rates of the two formulations were similar, indicating that the new formulation is both effective and safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study with lapatinib powder for oral suspension and the original tablet formulation in cancer patients. Koch, KM., Ferron-Brady, G., Lemmon, C., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Live Biotherapeutic Products, A Road Map for Safety Assessment. [2023]

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

Biosimilars: pharmacovigilance and risk management. [2013]

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

Healthy volunteer studies in Great Britain: the results of a survey into 12 months activity in this field. [2019]

5. Denmark pubmed.ncbi.nlm.nih.gov

Safety of biotechnological products. [2019]

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

Bioavailability and bioaccessibility of food bioactive compounds; overview and assessment by in vitro methods. [2021]

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

A perspective for biowaivers of human bioequivalence studies on the basis of the combination of the ratio of AUC to the dose and the biopharmaceutics classification system. [2011]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of the Similarity of Formulations and Excipients of Approved Generic Drug Products on In Vivo Bioequivalence for Putative Biopharmaceutics Classification System Class III Drugs. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

On the BCS biowaivers of orally disintegrating tablets. [2017]

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

Bioequivalence study with lapatinib powder for oral suspension and the original tablet formulation in cancer patients. [2018]