A Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PH100 Capsules in Healthy Adult Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Sodium (mmol/L)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
100mg Dose
1 x 100 mg PH100 capsule (n=6)
干预措施: PH100 100mg (Drug)
Control for 100mg Dose
1 placebo capsule (n=2)
干预措施: Placebo (Drug)
200mg Dose
1 x 200 mg PH100 capsule (n=6)
干预措施: PH100 200mg (Drug)
Control for 200mg Dose
1 placebo capsule (n=2)
干预措施: Placebo (Drug)
400mg Dose
2 x 200 mg PH100 capsules (n=6)
干预措施: PH100 400mg (Drug)
Control for 400mg Dose
2 placebo capsules (n=2)
干预措施: Placebo (Drug)
800mg Dose
4 x 200 mg PH100 capsules (n=6)
干预措施: PH100 800mg (Drug)
Control for 800mg Dose
4 placebo capsules (n=2)
干预措施: Placebo (Drug)
1200mg Dose
6 x 200 mg PH100 capsules (n=6)
干预措施: PH100 1200mg (Drug)
Control for 1200mg Dose
6 placebo capsules (n=2)
干预措施: Placebo (Drug)
1600mg Dose
8 x 200 mg PH100 capsules (n=6)
干预措施: PH100 1600mg (Drug)
Control for 1600mg Dose
8 placebo capsules (n=2)
干预措施: Placebo (Drug)
结局指标
主要结局
Sodium (mmol/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Hemoglobin (g/dL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Leukocytes (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Basophils (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Neutrophils (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Calcium (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Chloride (mmol/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Creatinine (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Albumin (g/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Glucose (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Leukocyte esterase (/uL)
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Incidence of treatment emergent adverse events
时间窗: 96 hours postdose
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.
Hematocrit (%)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Basophils/Leukocytes (%)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Platelets (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Serum Glucose (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Aspartate phosphatase (U/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Specific gravity
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Occult blood (/uL)
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Change from Baseline Body Temperature (degrees C)
时间窗: 2, 4, 48, 96 hours postdose
Safety Assessment in Vital Signs
QTcB interval (ms)
时间窗: 48 hours postdose
Safety Assessment in ECG
Erythrocytes (10^6/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Eosinophils/Leukocytes (%)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Lymphocytes (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Lymphocytes/Leukocytes (%)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Monocytes/Leukocytes (%)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Potassium (mmol/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Urate (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Monocytes (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Alkaline phosphatase (U/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Eosinophils (10^3/uL)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Neutrophils/Leukocytes (%)
时间窗: 48 hours postdose
Safety Assessment in Hematology
Blood urea nitrogen (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Alanine transaminase (U/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Total bilirubin (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
Lactate Dehydrogenase (U/L)
时间窗: 48 hours postdose
Safety Assessment in Serum Chemistry
pH
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Nitrite (Negative/Positive)
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Bilirubin (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Urobilinogen (mg/dL)
时间窗: 48 hours postdose
Safety Assessment in Urinalysis
Change from Baseline Diastolic Blood Pressure (mmHg)
时间窗: 2, 4, 48, 96 hours postdose
Safety Assessment in Vital Signs
Change from Baseline Pulse Rate (bpm)
时间窗: 2, 4, 48, 96 hours postdose
Safety Assessment in Vital Signs
Change from Baseline Respiration Rate (Breath/Min)
时间窗: 2, 4, 48, 96 hours postdose
Safety Assessment in Vital Signs
PR interval (ms)
时间窗: 48 hours postdose
Safety Assessment in ECG
QTcF interval (ms)
时间窗: 48 hours postdose
Safety Assessment in ECG
Change from Baseline Systolic Blood Pressure (mmHg)
时间窗: 2, 4, 48, 96 hours postdose
Safety Assessment in Vital Signs
ECG heart rate (bpm)
时间窗: 48 hours postdose
Safety Assessment in ECG
QRS complex (ms)
时间窗: 48 hours postdose
Safety Assessment in ECG
QT interval (ms)
时间窗: 48 hours postdose
Safety Assessment in ECG
次要结局
- 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 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 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.)