Phase I Study of PH100 (Ecklonia Cava Phlorotannins)

Safety Issues Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PH100 Capsules in Healthy Adult Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04335045
• Other study ID #: 13-01-01
• Status: Completed
• Phase: Phase 1
• Start date: September 25, 2013
• Est. completion date: December 8, 2014

Study information

• Verified date: April 2020
• Source: Phloronol Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This was a single-center, randomized, double-blind, placebo-controlled, single ascending dose study in healthy volunteers in which subjects received either placebo or a 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1600 mg dose of PH100 capsules (over-encapsulated tablets containing purified Ecklonia cava phlorotannins as an active ingredient) in escalating dose groups (six cohorts). A total of 48 subjects were enrolled. Each cohort comprised eight subjects. Within each cohort, six subjects received PH100 and two subjects received placebo. The first cohort was dosed as a single group with PH100 (100 mg) or placebo. The subsequent five cohorts were dosed sequentially with 200 mg, 400 mg, 800 mg, 1200 mg, and 1600 mg of PH100 or placebo. Safety and pharmacokinetic data were collected and evaluated following each cohort. Dose escalation occurred after review of the safety and pharmacokinetic data from the preceding cohort(s). Doses were administered with subjects in the fasted condition.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 8, 2014
• Est. primary completion date: December 8, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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;

• Voluntarily consented to participate in this study and provided their written informed consent prior to start of any study-specific procedures;

• Able to communicate with the Investigator, and understand and comply with the requirements of the protocol;

• Willing and able to remain in the study unit for the entire duration of the confinement period and return for an outpatient visit;

• Had screening blood pressure (measured sitting after 3 minutes rest) 140/90 mmHg. Out-of-range blood pressure could be repeated once; and

• Willing and able to swallow up to eight size AAA capsules with water at dose administration. Size AAA capsules are 0.642 inches (16.31 mm) in length and 0.450 inches (11.44 mm) in diameter).

Exclusion Criteria:

• 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;

• Had a history of substance abuse or treatment (including alcohol);

• Was a female who had a positive pregnancy test result or was nursing, lactating, or trying to become pregnant;

• Had a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates), alcohol, or cotinine;

• Had a positive test for hepatitis B surface antigen (HbSAg), hepatitis C antibody, or human immunodeficiency virus (HIV) at screening or had been previously treated for hepatitis B, hepatitis C, or HIV infection; or

• Had difficulty swallowing up to eight capsules.

Related Conditions & MeSH terms

• Safety Issues

Intervention

Drug:
• Placebo
1~8 Placebo capsule(s) corresponding to each PH100 dose
• PH100 100mg
1 x 100 mg PH100 oral capsule
• PH100 200mg
1 x 200 mg PH100 oral capsule
• PH100 400mg
2 x 200 mg PH100 oral capsules
• PH100 800mg
4 x 200 mg PH100 oral capsules
• PH100 1200mg
6 x 200 mg PH100 oral capsules
• PH100 1600mg
8 x 200 mg PH100 oral capsules

Locations

Country	Name	City	State
United States	Worldwide Clinical Trials Early Phase Services, LLC	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Phloronol Inc.	Worldwide Clinical Trials

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Hematocrit (%)	Safety Assessment in Hematology	48 hours postdose
Primary	Hemoglobin (g/dL)	Safety Assessment in Hematology	48 hours postdose
Primary	Erythrocytes (10^6/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Leukocytes (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Basophils (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Basophils/Leukocytes (%)	Safety Assessment in Hematology	48 hours postdose
Primary	Eosinophils (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Eosinophils/Leukocytes (%)	Safety Assessment in Hematology	48 hours postdose
Primary	Lymphocytes (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Lymphocytes/Leukocytes (%)	Safety Assessment in Hematology	48 hours postdose
Primary	Monocytes (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Monocytes/Leukocytes (%)	Safety Assessment in Hematology	48 hours postdose
Primary	Neutrophils (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Neutrophils/Leukocytes (%)	Safety Assessment in Hematology	48 hours postdose
Primary	Platelets (10^3/uL)	Safety Assessment in Hematology	48 hours postdose
Primary	Serum Glucose (mg/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Sodium (mmol/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Potassium (mmol/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Calcium (mg/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Chloride (mmol/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Blood urea nitrogen (mg/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Creatinine (mg/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Urate (mg/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Albumin (g/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Alkaline phosphatase (U/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Aspartate phosphatase (U/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Alanine transaminase (U/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Total bilirubin (mg/dL)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Lactate Dehydrogenase (U/L)	Safety Assessment in Serum Chemistry	48 hours postdose
Primary	Specific gravity	Safety Assessment in Urinalysis	48 hours postdose
Primary	pH	Safety Assessment in Urinalysis	48 hours postdose
Primary	Glucose (mg/dL)	Safety Assessment in Urinalysis	48 hours postdose
Primary	Nitrite (Negative/Positive)	Safety Assessment in Urinalysis	48 hours postdose
Primary	Leukocyte esterase (/uL)	Safety Assessment in Urinalysis	48 hours postdose
Primary	Occult blood (/uL)	Safety Assessment in Urinalysis	48 hours postdose
Primary	Bilirubin (mg/dL)	Safety Assessment in Urinalysis	48 hours postdose
Primary	Urobilinogen (mg/dL)	Safety Assessment in Urinalysis	48 hours postdose
Primary	Change from Baseline Systolic Blood Pressure (mmHg)	Safety Assessment in Vital Signs	2, 4, 48, 96 hours postdose
Primary	Change from Baseline Diastolic Blood Pressure (mmHg)	Safety Assessment in Vital Signs	2, 4, 48, 96 hours postdose
Primary	Change from Baseline Pulse Rate (bpm)	Safety Assessment in Vital Signs	2, 4, 48, 96 hours postdose
Primary	Change from Baseline Respiration Rate (Breath/Min)	Safety Assessment in Vital Signs	2, 4, 48, 96 hours postdose
Primary	Change from Baseline Body Temperature (degrees C)	Safety Assessment in Vital Signs	2, 4, 48, 96 hours postdose
Primary	ECG heart rate (bpm)	Safety Assessment in ECG	48 hours postdose
Primary	PR interval (ms)	Safety Assessment in ECG	48 hours postdose
Primary	QRS complex (ms)	Safety Assessment in ECG	48 hours postdose
Primary	QT interval (ms)	Safety Assessment in ECG	48 hours postdose
Primary	QTcB interval (ms)	Safety Assessment in ECG	48 hours postdose
Primary	QTcF interval (ms)	Safety Assessment in ECG	48 hours postdose
Secondary	Change in Blood Concentration of 8,8'-bieckol (ng/mL) by HPLC-MS	Pharmacokinetics of 8,8'-bieckol, a major compound of PH100, after single, ascending, oral doses (100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, and 1600 mg) of PH100 in normal healthy volunteers.	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.
Secondary	Change in Blood Concentration of dieckol (ng/mL) by HPLC-MS	Pharmacokinetics of 8,8'-bieckol, a major compound of PH100, after single, ascending, oral doses (100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, and 1600 mg) of PH100 in normal healthy volunteers.	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.
Secondary	Change in Blood Concentration of PFF-A (ng/mL) by HPLC-MS	Pharmacokinetics of 8,8'-bieckol, a major compound of PH100, after single, ascending, oral doses (100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, and 1600 mg) of PH100 in normal healthy volunteers.	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.