Study of rhPTH(1-84) in Japanese Healthy Subjects Compared With Matched Caucasian Healthy Adult Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03150108
• Date of registration: 01/05/2017
• Prospective Registration: Yes
• Primary sponsor: Shire
• Public title: Study of rhPTH(1-84) in Japanese Healthy Subjects Compared With Matched Caucasian Healthy Adult Subjects
• Scientific title: A Phase 1, Open-label, Randomized, Cross-over Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single Dose of rhPTH(1-84) Administered Subcutaneously in Japanese Healthy Subjects Compared With Matched Non-Hispanic, Caucasian Healthy Adult Subjects and to Assess Dose Proportionality of 3 Doses of rhPTH(1-84) in the Japanese Subjects
• Date of first enrolment: May 16, 2017
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03150108
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Shire Physician
• Affiliation: Shire

Key inclusion & exclusion criteria

Inclusion Criteria:

- Ability to voluntarily provide written, signed, and dated informed consent as
applicable to participate in the study.

- An understanding, ability, and willingness to fully comply with study procedures and
restrictions.

- Age 18-65 inclusive at the time of consent. The date of signature of the informed
consent is defined as the beginning of the screening period. This inclusion criterion
will only be assessed at the first screening visit.

- Subjects must be either:

- A subject of Japanese descent born in Japan, who has resided outside of Japan for
no longer than 5 years and is of Japanese parentage, defined as having 2 Japanese
parents, and 4 Japanese grandparents, all born in Japan.

- A non-hispanic, Caucasian subject who has 2 non-hispanic, Caucasian parents and 4
non-hispanic, Caucasian grandparents.

- Male or nonpregnant, nonlactating female who agrees to comply with any applicable
contraceptive requirements of the protocol or females of nonchildbearing potential.

- Considered "healthy" by the investigator. Healthy status is defined by absence of
evidence of any active or chronic disease following a detailed medical and surgical
history, a complete physical examination including vital signs, 12-lead
electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.

- Body mass index between 18.5 and 28 kilogram per square meter (kg/m^2), inclusive,
with a body weight greater than or equal to (>=) 45 kg (99 pounds [lbs]). This
inclusion criterion will only be assessed at the first screening visit.

- Willing and able to consume standardized meals during the confinement period of the
study. All subjects will be required to consume the identical meals on study days when
serial pharmacokinetic (PK) and pharmacodynamic (PD) blood samples are collected.

- A clinical safety laboratory parameter of hemoglobin greater than (>) 11.7 gram per
deciliter (g/dl) (females) or 13.1 g/dl (males) and less than (<) 16 g/dl (females) or
17.4 g/dl (males) or, if out of this range, deemed not clinically significant by the
principal investigator.

- Total serum calcium within laboratory normal limits.

- Serum parathyroid hormone (PTH) levels within laboratory normal limits.

Exclusion Criteria:

- 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
investigational product, or clinical or laboratory assessments.

- Current or relevant history of physical or psychiatric illness, any medical disorder
that may require treatment or make the subject unlikely to fully complete the study,
or any condition that presents undue risk from the investigational product or
procedures.

- Known or suspected intolerance or hypersensitivity to the investigational product(s),
closely-related compounds, or any of the stated ingredients.

- Significant illness, as judged by the investigator, within 2 weeks of the first dose
of investigational product.

- Known history of alcohol or other substance abuse within the last year.

- Donation of blood or blood products (Example (eg), plasma or platelets) within 60 days
prior to receiving the first dose of investigational product.

- Use of the following prior to administration of investigational product within:

- 30 days - loop diuretics, lithium, antacids, systemic corticosteroids (medical
judgment is required by the investigator. Primarily high doses of systemic
corticosteroids [eg, prednisone] should be excluded. Stable doses of
hydrocortisone [eg, as treatment for Addison's disease] may be acceptable).

- 3 months - calcitonin, cinacalcet hydrochloride, treatment with rhPTH(1-84) or
N-terminal PTH or PTH-related peptide fragments or analogs.

- For females: changes in hormone replacement therapy within 3 months are excluded.
Stable (=3 months) hormone replacement therapy is acceptable.

- 6 months - fluoride tablets, oral bisphosphonates, methotrexate, growth hormone,
digoxin, raloxifene or similar selective estrogen receptor modulators (SERMs).

- 12 months - intravenous bisphosphonates, drug or alcohol abuse, as determined by
the investigator.

- Confirmed systolic blood pressure (BP) >39 millimeter of mercury (mmHg) or <89 mmHg,
and diastolic BP >89 mmHg or <49 mmHg.

- Twelve-lead ECG demonstrating measure of time between the start of the Q wave and the
end of the T wave using Fridericia's formula in an electrocardiogram (QTcF) >450
milliseconds (msec) at screening. If QTcF exceeds 450 msec, the ECG should be repeated
2 more times and the average of the 3 QTcF values should be used to determine the
subject's eligibility.

- Positive screen for drugs of abuse at screening or drugs of abuse or alcohol on Day
-1.

- Male subjects who consume more than 21 units of alcohol per week or 3 units per day.
Female subjects who consume more than 14 units of alcohol per week or 2 units per day.
(1 alcohol unit=1 beer or 1 wine (5 ounce (oz) per 150 milliliter (mL)) or 1 liquor
(1.5oz/40 mL) or 0.75 oz alcohol).

- Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or
hepatitis C virus (HCV) antibody screen.

- Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing
products in any form (eg, gum, patch). Ex-users must report that they have stopped
using tobacco for at least 30 days prior to receiving the first dose of
investigational product.

- Routine consumption of more than 2 units of caffeine per day or subjects who
experience caffeine withdrawal headaches. (1 caffeine unit 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. Decaffeinated coffee, tea, or cola
are not considered to contain caffeine).

- Prior screen failure, randomization, participation, or enrollment in this study or
prior exposure to any exogenous PTH, PTH fragments or analogs.

- Current use of any medication (including over-the-counter, herbal, or homeopathic
preparations; with the exception of hormonal replacement therapy or hormonal
contraceptives and occasional use of ibuprofen and acetaminophen). Current use is
defined as use within 14 days


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypoparathyroidism

Intervention(s)

Drug: rhPTH(1-84)

Primary Outcome(s)

Baseline-adjusted Lambda_z of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline- Adjusted % of AUC(0-Inf) Extra of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted AUC(0-8) of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted AUC(Last) of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted Vdz/F of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted CL/F of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted t1/2 of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted Tmax of PTH(1-84) [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted AUC(0-inf) of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Baseline-adjusted Cmax of PTH(1-84) [Time Frame: 30 and 90 minutes (min) Pre-dose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (h) Post-dose]

Secondary Outcome(s)

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results Reported as Treatment-emergent Adverse Events (TEAEs) [Time Frame: Non-Hispanic Caucasians: 30 min pre-dose,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,24 h post-dose on Days 1,4,7 and 32 days after last dose]

Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Time Frame: From start of study drug administration to follow-up (up to 40 days)]

AUClast of Albumin-corrected Calcium, Serum Total Calcium and Phosphate Levels After Intake of PTH(1-84) [Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)]

Number of Participants Who Reported Positive to Anti-Parathyroid Hormone Antibodies [Time Frame: Non-Hispanic Caucasians: 30 min pre-dose,32 days post-dose Japanese Descents: 30 min pre-dose on Days 1,4,7 and 32 days after last dose]

Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Treatment-emergent Adverse Events (TEAEs) [Time Frame: Non-Hispanic Caucasians: 30 min pre-dose,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,24 h post-dose on Days 1,4,7 and 32 days after last dose]

Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment-emergent Adverse Events (TEAEs) [Time Frame: Non-Hispanic Caucasians: 30 min pre-dose,1,4,8,24 h,32 days post-dose Japanese Descents: 30 min pre-dose,1,4,8,24 h post-dose on Days 1,4,7 and 32 days after last dose]

Original Tmax of PTH(1-84) [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

TEmax After Intake of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels [Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)]

Emax of PTH(1-84) on Albumin-corrected Calcium, Serum Total Calcium and Serum Phosphate Levels [Time Frame: Non-Hispanic Caucasians: 30 mins predose, 4, 8 and 12 h (Day 1),24 h (Day 2) Japanese Descents: 30 mins predose, 4, 8 and 12 h (Days 1, 4, 7), 24 h (Days 2, 5, 8)]

Original AUClast of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Original Cmax of PTH(1-84) in Plasma [Time Frame: 30 and 90 min Pre-dose,10, 20, 30, 45 min, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 h Post-dose]

Secondary ID(s)

SHP634-102

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/07/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03150108