A Randomized, Open-label, Single-center, Single-dose Study to Evaluate the Relative Bioavailability of a New Formulation Compared With the Approved Formulation of Recombinant Human Parathyroid Hormone (rhPTH[1-84]) and to Assess Dose Linearity of the New Formulation in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Part II: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
研究概览
简要总结
The main aim of Part I of this study is to evaluate the relative bioavailability of a new formulation compared with the approved formulation when a single dose of rhPTH(1-84) is given to healthy volunteers. Bioavailability is the ability of a drug to be absorbed and used by the body. In Part II, the main aim is to assess the dose linearity of the new formulation.
Participants will receive 2 doses in Part I and 4 doses in Part II.
Participants need to visit their doctor approximately 14 days and 30 days after the last dose of study drug.
详细描述
This study will be conducted in two parts (Part I and Part II). Part I consists of two treatment periods with 2 sequences and part II consists of four treatment periods with 4 sequences. In Part I, relative bioavailability of Formulation A (Test: 100 microgram [mcg] rhPTH[1-84]) will be compared with Formulation B (Reference: 100 mcg rhPTH[1-84]). In Part II, dose linearity of the new formulation, Formulation A, of rhPTH (1-84) will be assessed based on 4 different dose levels as dose c - f (dose c = 25 mcg, dose d = 50 mcg, dose e = 75 mcg and f = 200 mcg). Both parts may be conducted concurrently.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must fulfill all of the following inclusion criteria to be eligible for participation in the study:
- •Healthy, adult, male or female, 18-65 years of age, inclusive, at screening. Attempts will be made to enroll at least 20% of each sex in each study part.
- •Continuous non-smoker who has not used nicotine containing products for at least 90 days prior to the first dosing and throughout the study, based on participant self-reporting.
- •Body mass index (BMI) greater than or equal to (>=) 18.5 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m2) at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee including the following:
- •Serum calcium, parathyroid hormone (PTH), phosphate, and magnesium within laboratory normal limits at screening and check-in.
- •Vitamin D (1,25(OH)2D3) levels between lower limit of normal and up to 1.5x Upper Limit of Normal (ULN).
- •Seated blood pressure Beats per minute (bpm) is >= 89/49 millimeters of mercury (mmHg) and <=139/89 mmHg at screening.
- •Seated pulse rate is >=40 bpm and <=99 bpm at screening.
- •QTcF interval is <=450 millisecond (msec) (males) or <= 470 msec (females) or ECG findings considered normal or not clinically significant by the Investigator or designee at screening.
- •Estimated creatinine clearance >= 80 milliliter per minute (mL/minute) at screening.
- •Agrees to comply with any applicable contraceptive requirements of the protocol.
- •Understands the study procedures in the ICF, be able to voluntarily provide written, signed, and dated informed consent, and be willing and able to comply with the protocol.
排除标准
- •Participants must not be enrolled in the study if they meet any of the following criteria:
- •Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study in the opinion of the Investigator or designee.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee.
- •History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the study drug, or clinical or laboratory assessments.
- •Participants who are at increased baseline risk for osteosarcoma such as participants with Paget's disease of bone or unexplained elevations of alkaline phosphatase (ALP), hereditary disorders predisposing to osteosarcoma or a prior history of external beam or implant radiation therapy involving the skeleton.
- •History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- •History or presence of alcoholism or drug abuse, in the opinion of the Investigator or designee, within the past 2 years prior to the first dosing.
- •Male participants who consume more than 21 units of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day. (1 alcohol unit=1 beer or 1 wine (5 ounces (oz)/150 in milliliters (mL) or 1 liquor (1.5 oz/40 mL) or 0.75 oz alcohol).
- •Positive urine drug or alcohol results at screening or check-in.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
- •History of abnormalities of calcium homeostasis including hyperparathyroidism, hypoparathyroidism, hyperthyroidism, Cushing's syndrome, hypercalcemia, hypocalcemia, osteoporosis, or any other calcium disorder.
- •Female participants who have a positive pregnancy test or who are lactating.
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
- •Has tattoo(s) or scarring at or near the site of injection or any other condition which may interfere with injection site examination, in the opinion of the Investigator or designee.
- •Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine withdrawal headaches. A unit of caffeine is contained in the following items: one 6 oz (180 mL) cup of coffee, two 12 oz (360 mL) cans of cola, one 12 oz cup of tea, three 1 oz (85 g) chocolate bars.
- •Prior screen failure, randomization, participation, or enrollment in this study or prior exposure to any exogenous PTH, PTH fragments or analogs 3 months prior to dosing with rhPTH(1-84).
- •Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements) Medication, Supplements, and Dietary Products) for the prohibited time period.
- •Has been on a diet incompatible with the study diet or had any substantial changes in eating habits, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study.
- •Donation of blood or significant blood loss within 60 days prior to the first dosing.
- •Plasma donation within 7 days prior to the first dosing.
- •Participation in another clinical study within 30 days or 5 half-lives of the study drug prior to the first dosing. The 30-day window or 5 half-lives will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Treatment Period 1 of the current study.
研究组 & 干预措施
Part I: Sequence AB
Participants will receive a single SC injection of 100 microgram (mcg) rhPTH(1-84) (Formulation A) on Day 1 of treatment period 1 followed by 100 mcg rhPTH(1-84) (Formulation B) on Day 1 of treatment period 2. A washout period of 96 hours will be maintained between each treatment period.
干预措施: rhPTH(1-84) (Drug)
Part I: Sequence BA
Participants will receive a single SC injection of 100 microgram (mcg) rhPTH(1-84) (Formulation B) on Day 1 of treatment period 1 followed by 100 mcg rhPTH(1-84) (Formulation A) on Day 1 of treatment period 2. A washout period of 96 hours will be maintained between each treatment period.
干预措施: rhPTH(1-84) (Drug)
Part II: Sequence CDEF
Participants will receive a single SC injection of 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 1 followed by 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 2 followed by 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 3 followed 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.
干预措施: rhPTH(1-84) (Drug)
Part II: Sequence DFCE
Participants will receive a single SC injection of 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 1 followed by 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 2 followed by 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 3 followed by 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.
干预措施: rhPTH(1-84) (Drug)
Part II: Sequence ECFD
Participants will receive a single SC injection of 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 1 followed by 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 2 followed by 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 3 followed by 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.
干预措施: rhPTH(1-84) (Drug)
Part II: Sequence FEDC
Participants will receive a single SC injection of 200 mcg (dose F) rhPTH(1-84) on Day 1 of treatment period 1 followed by 75 mcg (dose E) rhPTH(1-84) on Day 1 of treatment period 2 followed by 50 mcg (dose D) rhPTH(1-84) on Day 1 of treatment period 3 followed by 25 mcg (dose C) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours will be maintained between each treatment period 1,2,3 and 4.
干预措施: rhPTH(1-84) (Drug)
结局指标
主要结局
Part II: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
时间窗: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
Cmax referred to the maximum (or peak) concentration that a drug achieved in the body after the drug had been administrated.
Part II: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)
时间窗: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.
Part I: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)
时间窗: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
AUCinf was the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC was be used as a measure of drug exposure. It was derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Part II: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)
时间窗: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
AUCinf was the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC was be used as a measure of drug exposure. It was derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Part I: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)
时间窗: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.
Part I: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
时间窗: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
Cmax referred to the maximum (or peak) concentration that a drug achieved in the body after the drug had been administrated.
Number of Participants With Clinically Significant Changes in Vital Signs Values
时间窗: From start of study drug administration up to Day 34
Vital sign assessments included systolic and diastolic blood pressure, pulse rate and body temperature. Any change in vital signs which are deemed clinically significant by the investigator were reported.
次要结局
- Part I and II: Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From start of study drug administration up to Day 34)
- Part I and II: Number of Participants With Clinically Significant Changes in Clinical Laboratory Values(From start of study drug administration up to Day 34)
- Part I and II: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters Reported as TEAEs(From start of study drug administration up to Day 34)