A Study to Evaluate the Bioavailability of Teduglutide Administered Subcutaneously by Syringe Injection Versus Pen Injector in Healthy Adult Participants

Healthy Volunteers Clinical Trial

Official title:

A Randomized, Open-label, Two-treatment, Two-period, Single-dose, Crossover Study to Evaluate the Bioavailability of Teduglutide Administered Subcutaneously by Syringe Injection Versus Pen Injector in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04465396
• Other study ID #: TAK-633-1001
• Status: Completed
• Phase: Phase 1
• Start date: January 13, 2021
• Est. completion date: August 20, 2021

Study information

• Verified date: March 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the bioavailability of teduglutide administered as a single subcutaneous (SC) fixed dose (depending upon participant weightband assignment) delivered by a syringe injection and the same fixed dose delivered by the pen injector in healthy participants.

Description:

This is a 2-period crossover study and consists of two cohorts. Cohort 1 consists of participant's with greater than or equal to (>=) 40.0 kilogram (kg) to lesser than or equal to (<=) 75.0 kg of weight and Cohort 2 consists of participant's with greater than (>) 75.0 kg to <= 120.0 kg of weight. Participants in each cohort will be randomized to 1 of 2 treatment sequences AB or BA. Randomization will be stratified by injection site (i.e., thigh, abdomen, and arm) within each cohort.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 20, 2021
• Est. primary completion date: August 20, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

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

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

• Aged 18 - 45 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.

• Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing 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 full physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, coagulation (as appropriate), serum chemistry, and urinalysis.

• Body mass index (BMI) >= 18.0 and l<=32.0 kilogram per square meter (kg/m^2) at screening. Body weight for a participant in Cohort 1 will be >= 40.0 kg to <= 75.0 kg, and body weight for a participant in Cohort 2 will be > 75.0 kg to <= 120.0 kg, inclusive. This inclusion criterion will be assessed at the screening visit and confirmed at first check-in.

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 participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.

• Positive PCR (polymerase chain reaction) test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), either with the absence or presence of the clinical symptoms of Coronavirus disease 2019 (COVID-19).

• Known or suspected intolerance or hypersensitivity to teduglutide, closely-related compounds, or any of the stated ingredients.

• Significant illness, as judged by the investigator, within 2 weeks of the first dose of teduglutide.

• Known history of alcohol or other substance abuse within the last year prior to screening.

• Donation of blood or blood products (e.g. plasma or platelets) within 60 days prior to receiving the first dose of teduglutide.

• Pregnant or lactating female.

• Within 30 days prior to the first dose of teduglutide:

1. Have used an investigational product (if elimination half-life is lesser than [<] 6 days, otherwise 5 half-lives)

2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's (or designee's) opinion, may impact this study

3. Have had any substantial changes in eating habits, as assessed by the investigator (or designee)

• Use of dipeptidyl peptidase 4 inhibitors within 30 days or 5 half-lives, whichever is greater, prior to administration of the first dose of teduglutide.

• Confirmed systolic blood pressure > 140 millimeter of mercury (mmHg) or < 90 mmHg, and diastolic blood pressure > 90 mmHg or < 40 mmHg at screening.

• Twelve-lead electrocardiogram (ECG) demonstrating QTcF > 450 milliseconds (msec) at screening. If the QTcF exceeds the aforementioned limits, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participants eligibility.

• Positive screen for drugs of abuse or alcohol at screening and at each check-in.

• Male participants who consume more than 21 units of alcohol per week or regularly consume more than 3 units per day. Female participants who consume more than 14 units of alcohol per week or regularly consume more than 2 units per day. (1 alcohol unit=150 milliliter [mL] of wine, or 360 mL of beer, or 45 mL of 45 percent [%] alcohol).

• Positive Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen at screening.

• Use of tobacco in any form (e.g. smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch) based on participant self-reporting. Ex-users must report that they have stopped using tobacco for at least 3 months prior to receiving the first dose of teduglutide.

• Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6 ounce (oz) (180 mL) cup of coffee, two 12 oz (360 mL) cans of cola, one 12 oz (360 mL) cup of tea, three 1 oz (85 gram [g]) chocolate bars.

• Prior screen failure, randomization, participation, or enrollment in this study, or prior exposure to any Glucagon-like peptide 2 (GLP-2) analogs.

• Presence of lesions, rashes, tattoos, and moles etc. on administration sites not allowing adequate conduct of injection site reaction and injection site injury assessment

• Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of occasional use of ibuprofen [1.2 g per 24 hour period] or acetaminophen [2 g per 24 hour period]). Current use is defined as use within 14 days of the first dose of teduglutide and throughout the study.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Teduglutide
Participants received 3 mg or 4 mg of Teduglutide SC syringe injection followed by pen injector or vice versa depending upon the treatment sequence AB or BA on Day 1 of Treatment Periods 1 and 2.

Device:
• Syringe Injection
Teduglutide was administered using syringe.
• Pen injector
Teduglutide was administered using pen injector.

Locations

Country	Name	City	State
United States	Celerion	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Shire	Takeda Development Center Americas, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Primary	Maximum Observed Plasma Concentration (Cmax) of Teduglutide	Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Primary	Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site	AUC0-last of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site	Cmax of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site	AUC0-infinity of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Apparent Total Body Clearance (CL/F) of Teduglutide	CL/F for extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Apparent Volume of Distribution (Vz/F) of Teduglutide	Vz/F associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened at the time of or after study drug administration. Number of participants with TEAEs included injection site reactions and injection site injury assessments.	From the start of study drug administration up to follow-up (up to 42 days)
Secondary	Number of Participants With Clinically Significant Change in Vital Signs	Vital signs included body temperature, respiratory rate, blood pressure, and heart rate.	From the start of study drug administration up to follow-up (up to 42 days)
Secondary	Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments	Clinical laboratory assessments included hematology, serum chemistry, coagulation, and urinalysis. Changes in laboratory values may be considered as AE if they were judged to be clinically significant.	From the start of study drug administration up to follow-up (up to 42 days)
Secondary	Number of Participants With Clinically Significant Changes in Physical Examinations	Physical examination included examination of respiratory, cardiovascular, and gastrointestinal system.	From the start of study drug administration up to follow-up (up to 42 days)
Secondary	Number of Participants With Device Malfunction	Number of participants with device malfunction was assessed and reported. The site staff reported any malfunctions whilst using the device.	Day 1

External Links

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