Phase I Study of PH100 (Ecklonia Cava Phlorotannins)

NCT04335045 | Completed Phase 1 FDA Drug

• 1 other identifier: 13-01-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to determine the safety and tolerability of PH100, a purified phlorotannins from a brown alga Ecklonia cava and the pharmacokinetics of its major compounds 8,8'-bieckol, dieckol, and phlorofucofuroeckol A (PFF-A), after single, ascending, oral doses of PH100 Capsules (over-encapsulated tablets) in healthy adult volunteers.

Conditions

Safety Issues

Keywords

Safety; Tolerability; Pharmacokinetics; PH100; Ecklonia cava; Phlorotannin

Outcome Measures

Primary Outcomes (49)

• Incidence of treatment emergent adverse events

  Subjects were instructed to inform the study physician and/or research personnel of any AEs that occurred at any time during the study. Subjects were monitored for AEs from the beginning of confinement through the end-of-study visit (96 hours after dose administration). Reported or observed AEs were documented and followed to resolution.

  96 hours postdose

• Hematocrit (%)

  Safety Assessment in Hematology

  48 hours postdose

• Hemoglobin (g/dL)

  Safety Assessment in Hematology

  48 hours postdose

• Erythrocytes (10^6/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Leukocytes (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Basophils (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Basophils/Leukocytes (%)

  Safety Assessment in Hematology

  48 hours postdose

• Eosinophils (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Eosinophils/Leukocytes (%)

  Safety Assessment in Hematology

  48 hours postdose

• Lymphocytes (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Lymphocytes/Leukocytes (%)

  Safety Assessment in Hematology

  48 hours postdose

• Monocytes (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Monocytes/Leukocytes (%)

  Safety Assessment in Hematology

  48 hours postdose

• Neutrophils (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Neutrophils/Leukocytes (%)

  Safety Assessment in Hematology

  48 hours postdose

• Platelets (10^3/uL)

  Safety Assessment in Hematology

  48 hours postdose

• Serum Glucose (mg/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Sodium (mmol/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Potassium (mmol/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Calcium (mg/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Chloride (mmol/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Blood urea nitrogen (mg/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Creatinine (mg/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Urate (mg/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Albumin (g/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Alkaline phosphatase (U/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Aspartate phosphatase (U/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Alanine transaminase (U/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Total bilirubin (mg/dL)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Lactate Dehydrogenase (U/L)

  Safety Assessment in Serum Chemistry

  48 hours postdose

• Specific gravity

  Safety Assessment in Urinalysis

  48 hours postdose

• pH

  Safety Assessment in Urinalysis

  48 hours postdose

• Glucose (mg/dL)

  Safety Assessment in Urinalysis

  48 hours postdose

• Nitrite (Negative/Positive)

  Safety Assessment in Urinalysis

  48 hours postdose

• Leukocyte esterase (/uL)

  Safety Assessment in Urinalysis

  48 hours postdose

• Occult blood (/uL)

  Safety Assessment in Urinalysis

  48 hours postdose

• Bilirubin (mg/dL)

  Safety Assessment in Urinalysis

  48 hours postdose

• Urobilinogen (mg/dL)

  Safety Assessment in Urinalysis

  48 hours postdose

• Change from Baseline Systolic Blood Pressure (mmHg)

  Safety Assessment in Vital Signs

  2, 4, 48, 96 hours postdose

• Change from Baseline Diastolic Blood Pressure (mmHg)

  Safety Assessment in Vital Signs

  2, 4, 48, 96 hours postdose

• Change from Baseline Pulse Rate (bpm)

  Safety Assessment in Vital Signs

  2, 4, 48, 96 hours postdose

• Change from Baseline Respiration Rate (Breath/Min)

  Safety Assessment in Vital Signs

  2, 4, 48, 96 hours postdose

• Change from Baseline Body Temperature (degrees C)

  Safety Assessment in Vital Signs

  2, 4, 48, 96 hours postdose

• ECG heart rate (bpm)

  Safety Assessment in ECG

  48 hours postdose

• PR interval (ms)

  Safety Assessment in ECG

  48 hours postdose

• QRS complex (ms)

  Safety Assessment in ECG

  48 hours postdose

• QT interval (ms)

  Safety Assessment in ECG

  48 hours postdose

• QTcB interval (ms)

  Safety Assessment in ECG

  48 hours postdose

• QTcF interval (ms)

  Safety Assessment in ECG

  48 hours postdose

Secondary Outcomes (3)

• Change in Blood Concentration of 8,8'-bieckol (ng/mL) by HPLC-MS

  at 0, 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 96 hours after dosing.

• Change in Blood Concentration of dieckol (ng/mL) by HPLC-MS

  at 0, 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 96 hours after dosing.

• Change in Blood Concentration of PFF-A (ng/mL) by HPLC-MS

  at 0, 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 96 hours after dosing.

Study Arms (12)

100mg Dose

ACTIVE COMPARATOR

1 x 100 mg PH100 capsule (n=6)

Drug: PH100 100mg

Control for 100mg Dose

PLACEBO COMPARATOR

1 placebo capsule (n=2)

Drug: Placebo

200mg Dose

ACTIVE COMPARATOR

1 x 200 mg PH100 capsule (n=6)

Drug: PH100 200mg

Control for 200mg Dose

PLACEBO COMPARATOR

1 placebo capsule (n=2)

Drug: Placebo

400mg Dose

ACTIVE COMPARATOR

2 x 200 mg PH100 capsules (n=6)

Drug: PH100 400mg

Control for 400mg Dose

PLACEBO COMPARATOR

2 placebo capsules (n=2)

Drug: Placebo

800mg Dose

ACTIVE COMPARATOR

4 x 200 mg PH100 capsules (n=6)

Drug: PH100 800mg

Control for 800mg Dose

PLACEBO COMPARATOR

4 placebo capsules (n=2)

Drug: Placebo

1200mg Dose

ACTIVE COMPARATOR

6 x 200 mg PH100 capsules (n=6)

Drug: PH100 1200mg

Control for 1200mg Dose

PLACEBO COMPARATOR

6 placebo capsules (n=2)

Drug: Placebo

1600mg Dose

ACTIVE COMPARATOR

8 x 200 mg PH100 capsules (n=6)

Drug: PH100 1600mg

Control for 1600mg Dose

PLACEBO COMPARATOR

8 placebo capsules (n=2)

Drug: Placebo

Interventions

Placebo DRUG

1\~8 Placebo capsule(s) corresponding to each PH100 dose

Control for 100mg Dose; Control for 1200mg Dose; Control for 1600mg Dose; Control for 200mg Dose; Control for 400mg Dose; Control for 800mg Dose

PH100 100mg DRUG

1 x 100 mg PH100 oral capsule

100mg Dose

PH100 200mg DRUG

1 x 200 mg PH100 oral capsule

200mg Dose

PH100 400mg DRUG

2 x 200 mg PH100 oral capsules

400mg Dose

PH100 800mg DRUG

4 x 200 mg PH100 oral capsules

800mg Dose

PH100 1200mg DRUG

6 x 200 mg PH100 oral capsules

1200mg Dose

PH100 1600mg DRUG

8 x 200 mg PH100 oral capsules

1600mg Dose

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or nonpregnant, nonbreastfeeding female;
• Between 40 and 75 years of age (inclusive);
• Body mass index (BMI) between 18 and 30 kg/m2 (inclusive), and minimum weight of 50 kg (110 lbs);
• If female, subject was considered postmenopausal or surgically sterile and had status confirmed by one of the following:
• Physiologicallypostmenopausalbasedonnomensesforatleast2years(not due to lactational amenorrhea) and follicle stimulating hormone (FSH) levels equal to or greater than 40.0 mIU/mL at screening; or
• Bilateraloophorectomy,hysterectomy,orbilateraltuballigation(post 6 months). Or
• If female and of childbearing potential, subject agreed to use one of the following forms of birth control from 3 months prior through 12 days after study drug administration:
• Vasectomizedpartner(atleast6monthspriortodosing);
• Doublebarrier(diaphragmwithspermicide;condomswithspermicide);
• Intrauterinedevice(IUD);
• Abstinence(agreedtouseadoublebarriermethodiftheybecamesexually active during the study);
• Implantedorintrauterinehormonalcontraceptives;or
• Oral,patch,orinjectedcontraceptives,orvaginalhormonaldevice (i.e. NuvaRing®).
• If male, subject had a documented vasectomy or agreed to use a double-barrier local contraception (i.e., condom with spermicide) when engaging in sexual activity with women of childbearing potential from prior to the first dose of study drug through 28 days after the last dose of study drug;
• If male, subject agreed to refrain from sperm donation from prior to the first dose of study drug through 28 days after the last dose of study drug;

You may not qualify if:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, GI, endocrine (including thyroid), immunologic, dermatologic, neurologic, oncologic, respiratory, lymphatic, musculoskeletal, genitourinary, infective, inflammatory, connective tissue, or psychiatric disease or disorder or any other condition that, in the opinion of the Investigator, would have jeopardized the safety of the subject or the validity of the study results;
• Clinically relevant history or presence of cardiac arrhythmia, narrow angle glaucoma, benign prostatic hypertrophy (men only), Hashimoto's thyroiditis, lymphocytic thyroiditis, or uncontrolled diabetes;
• Had a clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening;
• History or presence of allergic or adverse response to PH100 (product names: Seapolynol, Fibroboost, Fibronol, Seanol Longevity Plus, Circulate, Alginol, PC Ecklonia Cava, Seanol, Seanol-F, Seanol-EX, Seanol-TX, Venusen, Memories with Seanol-P, Astaxanthol, Brilliant Vision with Seanol-P, Gly-Control, Gyne-Andro-Plex, Lipid Balance, Seanol with Broccoraphanin, and Marine D3) or related drugs;
• Had used PH100 (product names: Seapolynol, Fibroboost, Fibronol, Seanol Longevity Plus, Circulate, Alginol, PC Ecklonia Cava, Seanol, Seanol-F, Seanol-EX, Seanol-TX, Venusen, Memories with Seanol-P, Astaxanthol, Brilliant Vision with Seanol-P, Gly-Control, Gyne-Andro-Plex, Lipid Balance, Seanol with Broccoraphanin, and Marine D3) as a supplement within 30 days prior to the first dose of study medication;
• Had been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication;
• Had donated blood or plasma within 30 days prior to the first dose of study medication;
• Had participated in another clinical trial (randomized subjects only) within 30 days prior to first dose of study medication;
• Had used any over-the-counter (OTC) medication, including nutritional supplements, within 5 half-lives or 14 days (whichever was longer) prior to the first dose of study medication;
• Had used any prescription medication, except hormonal contraceptives for women of childbearing potential or hormone replacement therapy, within 5 half-lives or 14 days (whichever was longer) prior to the first dose of study medication;
• Had ingested drinks or foods containing grapefruit or St. John's Wort within 14 days prior to the first dose of study medication;
• Had been treated with any known drugs that are moderate or strong inhibitors/inducers of CYP enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication and that in the Investigator's judgment may have impacted subject safety or the validity of the study results;
• Had discontinued the use of implanted, intrauterine, or injected hormonal contraceptives less than 6 months prior to the first dose of study medication;
• Had discontinued the use of oral, patch, or vaginal hormonal contraceptives less than 1 month prior to the first dose of study medication;
• Had smoked or used tobacco products within 6 months prior to the first dose of study medication;

Sponsors & Collaborators

• Phloronol Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (1)

Worldwide Clinical Trials Early Phase Services, LLC

San Antonio, Texas, 78217, United States

Location

Study Officials

• George J. Atiee, MD

  Worldwide Clinical Trials Early Phase Services, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-center, randomized, double-blind, placebo-controlled, single ascending dose study

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 6, 2020
• Study Start: September 25, 2013
• Primary Completion: December 8, 2014
• Study Completion: December 8, 2014
• Last Updated: April 6, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)