Clinical trial NCT04335045: Phase I Study of PH100 (Ecklonia Cava Phlorotannins)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety Issues
Keywords: Safety
Tolerability
Pharmacokinetics
PH100
Ecklonia cava
Phlorotannin
Lead sponsor: Phloronol Inc.
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2020-04-06
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single-center, randomized, double-blind, placebo-controlled, single ascending dose study
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment emergent adverse events
timeFrame: 96 hours postdose
measure: Hematocrit (%)
timeFrame: 48 hours postdose
measure: Hemoglobin (g/dL)
timeFrame: 48 hours postdose
measure: Erythrocytes (10^6/uL)
timeFrame: 48 hours postdose
measure: Leukocytes (10^3/uL)
timeFrame: 48 hours postdose
measure: Basophils (10^3/uL)
timeFrame: 48 hours postdose
measure: Basophils/Leukocytes (%)
timeFrame: 48 hours postdose
measure: Eosinophils (10^3/uL)
timeFrame: 48 hours postdose
measure: Eosinophils/Leukocytes (%)
timeFrame: 48 hours postdose
measure: Lymphocytes (10^3/uL)
timeFrame: 48 hours postdose
measure: Lymphocytes/Leukocytes (%)
timeFrame: 48 hours postdose
measure: Monocytes (10^3/uL)
timeFrame: 48 hours postdose
measure: Monocytes/Leukocytes (%)
timeFrame: 48 hours postdose
measure: Neutrophils (10^3/uL)
timeFrame: 48 hours postdose
measure: Neutrophils/Leukocytes (%)
timeFrame: 48 hours postdose
measure: Platelets (10^3/uL)
timeFrame: 48 hours postdose
measure: Serum Glucose (mg/dL)
timeFrame: 48 hours postdose
measure: Sodium (mmol/L)
timeFrame: 48 hours postdose
measure: Potassium (mmol/L)
timeFrame: 48 hours postdose
measure: Calcium (mg/dL)
timeFrame: 48 hours postdose
measure: Chloride (mmol/L)
timeFrame: 48 hours postdose
measure: Blood urea nitrogen (mg/dL)
timeFrame: 48 hours postdose
measure: Creatinine (mg/dL)
timeFrame: 48 hours postdose
measure: Urate (mg/dL)
timeFrame: 48 hours postdose
measure: Albumin (g/dL)
timeFrame: 48 hours postdose
measure: Alkaline phosphatase (U/L)
timeFrame: 48 hours postdose
measure: Aspartate phosphatase (U/L)
timeFrame: 48 hours postdose
measure: Alanine transaminase (U/L)
timeFrame: 48 hours postdose
measure: Total bilirubin (mg/dL)
timeFrame: 48 hours postdose
measure: Lactate Dehydrogenase (U/L)
timeFrame: 48 hours postdose
measure: Specific gravity
timeFrame: 48 hours postdose
measure: pH
timeFrame: 48 hours postdose
measure: Glucose (mg/dL)
timeFrame: 48 hours postdose
measure: Nitrite (Negative/Positive)
timeFrame: 48 hours postdose
measure: Leukocyte esterase (/uL)
timeFrame: 48 hours postdose
measure: Occult blood (/uL)
timeFrame: 48 hours postdose
measure: Bilirubin (mg/dL)
timeFrame: 48 hours postdose
measure: Urobilinogen (mg/dL)
timeFrame: 48 hours postdose
measure: Change from Baseline Systolic Blood Pressure (mmHg)
timeFrame: 2, 4, 48, 96 hours postdose
measure: Change from Baseline Diastolic Blood Pressure (mmHg)
timeFrame: 2, 4, 48, 96 hours postdose
measure: Change from Baseline Pulse Rate (bpm)
timeFrame: 2, 4, 48, 96 hours postdose
measure: Change from Baseline Respiration Rate (Breath/Min)
timeFrame: 2, 4, 48, 96 hours postdose
measure: Change from Baseline Body Temperature (degrees C)
timeFrame: 2, 4, 48, 96 hours postdose
measure: ECG heart rate (bpm)
timeFrame: 48 hours postdose
measure: PR interval (ms)
timeFrame: 48 hours postdose
measure: QRS complex (ms)
timeFrame: 48 hours postdose
measure: QT interval (ms)
timeFrame: 48 hours postdose
measure: QTcB interval (ms)
timeFrame: 48 hours postdose
measure: QTcF interval (ms)
timeFrame: 48 hours postdose
Secondary outcomes:
measure: Change in Blood Concentration of 8,8'-bieckol (ng/mL) by HPLC-MS
timeFrame: 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.
measure: Change in Blood Concentration of dieckol (ng/mL) by HPLC-MS
timeFrame: 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.
measure: Change in Blood Concentration of PFF-A (ng/mL) by HPLC-MS
timeFrame: 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.
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials Early Phase Services, LLC
state: Texas
Study officials:
affiliation: Worldwide Clinical Trials Early Phase Services, LLC
name: George J. Atiee, MD
role: PRINCIPAL_INVESTIGATOR
References: