AGN-Cogni.Q Acute Dose Safety and Pharmacokinetics Dose-Response in Prostate Cancer Patients

Angelica Herbal Supplement AGN-Cogni.Q Acute Dose Safety and Pharmacokinetics (PK) Dose-Response in Prostate Cancer Patients (PK Dose Trial)

This study is to obtain acute dose safety and pharmacokinetics/pharmacodynamics (PK/PD) data in a dose-response trial in prostate cancer patients.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: AGN-Cogni.Q

Detailed Description

The long-term goal of the study is to conduct human clinical trials to test Angelica gigas Nakai (AGN) root alcoholic extract herbal supplement product (AGN-Cogni.Q, or Cogni.QTM, made with INM®176 proprietary ingredient, Quality of Life Laboratories, Purchase, NY) as a safe and potential efficacious modality for prostate cancer interception akin to secondary prevention to delay hormonal therapy or avoid it entirely after patients have developed recurrent disease following their standard of care (SOC) surgery and radiation curative treatment. The acute dose safety and pharmacokinetics (PK) and pharmacodynamics (PD) information in the target patient population from the current proposed acute PK dose-response trial will inform the optimal design and execution of the longer-term safety and efficacy (phase I/II) trials.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willingness and ability to give informed consent.
2. Agree to comply with all study procedures and attend all study visits to the best of their ability.
3. Male with age >=40 years.

4. History of prostate cancer diagnosis. Subjects with history of neuroendocrine or small cell prostate cancer will be excluded. Subjects are eligible if meet one or more of the below criteria:

   1. Patients treated forprostate cancer and no detectable disease on imaging and clinical determination are eligible for enrollment, regardless of risk category.
   2. Patients in the low-risk and favorable intermediate-risk groups who are not currently receiving any treatment or have declined any treatment.
5. Not on concurrent androgen deprivation therapy.
6. ECOG performance status 0-2.
7. Life expectancy of greater than 12 months.

8. Subjects must have normal liver and kidney function as defined below:

   • a) total bilirubin within normal institutional limits,
   • b) AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal,
   • c) Creatinine within 1.5 ULN of institutional limits OR creatinine clearance > 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
   • d) Adequate bone marrow function (Hgb ≥ 9.0 g/dL, Platelets ≥ 100 x 109/L, absolute neutrophil count (ANC) of ≥ 1.5 x 109/L), except for subjects with a history of chronic benign neutropenia, where an ANC of ≥ 1.0 x 109/L are eligible.
9. Subjects must agree to use two medically accepted method of contraception and must agree to continue use this method while on the trial and through at least one week after the last dose of study drug. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD) known to have a failure rate of less than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) withdrawal, spermicides only, or lactational amenorrhea are not acceptable methods of contraception.
10. Subjects must stop the CYP3A4 and CYP2C19 strong inhibitors or inducers 2 weeks prior to the start of the study and during the study.
11. Subjects currently taking herbal supplements containing AGN extract, including CognI.Q, Decursinol-50, Ache Action, Fast-Acting Joint Formula, EstroG-100/Profemin must discontinue these or any other supplements containing these products 4 weeks prior to starting study drug.

Exclusion Criteria:

1. Subjects with distant metastatic cancer. Node positive prostate cancer patients are allowed after completion of treatment.
2. Subjects who are receiving chemotherapy, or oral TKI, or immunotherapy (checkpoint inhibitor).
3. Subjects who are receiving any other investigational agents.
4. Uncontrolled intercurrent illness that would limit compliance with study requirements.
5. All vulnerable patient populations.
6. History of New York Heart Association Class III or IV heart failure, history of a myocardial infarction within 6 months, any uncontrolled cardiac arrhythmia, or any other cardiac related problem that would be considered a contraindication for participation in the opinion of the treating physician.
7. Use of androgen deprivation therapy (ADT) or anti-androgen therapy including LHRH agonist, antagonist, GNRH analogs, and antiandrogens.
8. Subjects who are taking Warfarin/Coumadin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AGN-Cogni.Q; Dose level +1 (800 mg, 4 Cogni.Q capsules, Fast at least 2 h before dose and 1 h after) Dose level +2 (1,200 mg, 6 Cogni.Q capsules, Fast at least 2 h before dose and 1 h after) Dose level +3 (1,600 mg, 8 Cogni.Q capsules, Fast at least 2 h before dose and 1 h after)	Drug: AGN-Cogni.Q; Herbal dietary supplement products containing/based on AGN alcoholic extracts (including CognI.Q; Decursinol-50TM, GWB78®, Ache Action, Fast-Acting Joint Formula, EstroG-100/Profemin) are marketed in the US for memory enhancement, pain relief and for women's post-menopausal symptom management.; Other Names: INM®176

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Safety Via Electrocardiography (EKG)	Evaluation of cardiac rhythm and repolarization using 12-lead EKG to identify any treatment-emergent abnormalities. Unit of Measure: Number of participants with treatment-emergent EKG abnormalities.	Baseline (pre-dose) and 5 hours post-dose on each dosing day and at 24 hours (Up to 5 weeks).
Safety Blood Laboratory Tests	Evaluation of hematological and metabolic safety via Complete Blood Count (CBC) with differential, Comprehensive Metabolic Panel (CMP), and coagulation tests (INR, PT, PTT) to identify any treatment-emergent abnormalities.	24 hours post-dose and prior to each subsequent dose level (Up to 5 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Peak Plasma Concentration (Cmax) of D, DA, and DOH	To determine the Cmax for decursin (D), decursinol angelate (DA), and their metabolite decursinol (DOH) following a single dose. Peak concentration is estimated from blood samples collected at 0, 2, 3, 4, 5, 6, 7, and 24 hours post-dose.	0 to 24 hours post-dose for each dosing visit (Up to 5 weeks)
Plasma Concentration Versus Time Curve (AUC)	Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24h) for decursin (D), decursinol angelate (DA), and their metabolite decursinol (DOH). AUC is calculated using the trapezoidal rule from blood samples collected at 0, 2, 3, 4, 5, 6, 7, and 24 hours post-dose.	0 to 24 hours post-dose for each dosing visit (Up to 5 weeks)
Change From Baseline in NK, CD4+ T, and CD8+ T Cell Percentages at 24 Hours.	The percentage of specific immune cell populations (NK cells, CD4+ T cells, and CD8+ T cells) within the total lymphocyte pool was measured using flow cytometric quantitation. Change is evaluated by comparing blood samples taken at Baseline (0h) to Day 2 (24 hours ± 2 hours) following administration of each AGN-CognI.Q dose.	Baseline (0 hours) and Day 2 (24 hours post-dose).
Body Temperature Measurements From Baseline Through 24 Hours Post-dose	Body temperature was recorded to monitor safety and physiological response. Measurements were taken via tympanic thermometer at baseline (0 hours) and at 2, 3, 4, 5, 6, 7 and 24 hours (±2 hours) following the administration of each AGN-CognI.Q dose.	Baseline (0 hours) and 24 hours post-dose.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Evaluation of clinical safety and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From first dose of study drug to 4 weeks (± 7 days) following the last dose.

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Monika Joshi, MD, Penn State Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2023
• Primary Completion (Actual): February 15, 2025
• Study Completion (Actual): February 15, 2025

Study Registration Dates

• First Submitted: May 5, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: pharmacokinetics; Angelica gigas Nakai; INM 176
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PSCI-21-173; R01CA260901 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All research materials and data, generated by this grant, will be distributed freely or deposited into a repository/stock center making them available to the broader scientific community, either before or immediately after publication.
• IPD Sharing Time Frame: One year after publication
• IPD Sharing Access Criteria: Deidentified individual participant data will be available to qualified researchers upon reasonable request to the study investigators, following publication and in accordance with institutional and NIH data sharing policies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No