Clinical trial NCT04465396: A Study to Evaluate the Bioavailability of Teduglutide Administered Subcutaneously by Syringe Injection Versus Pen Injector in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2020-07-10
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Teduglutide
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide
timeFrame: 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 outcomes:
measure: 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
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site
timeFrame: 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
measure: Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide
timeFrame: 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
measure: Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide
timeFrame: 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
measure: Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide
timeFrame: 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
measure: Apparent Total Body Clearance (CL/F) of Teduglutide
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of Teduglutide
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the start of study drug administration up to follow-up (up to 42 days)
measure: Number of Participants With Clinically Significant Change in Vital Signs
timeFrame: From the start of study drug administration up to follow-up (up to 42 days)
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
timeFrame: From the start of study drug administration up to follow-up (up to 42 days)
measure: Number of Participants With Clinically Significant Changes in Physical Examinations
timeFrame: From the start of study drug administration up to follow-up (up to 42 days)
measure: Number of Participants With Device Malfunction
timeFrame: Day 1
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: