Ambulatory Blood Pressure Monitoring in Oral Testosterone Undecanoate (TU, LPCN 1021) Treated Hypogonadal Men

Study Overview
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Brief Summary
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This is an open-label, multi-center, single arm study evaluating the blood pressure (BP) changes from baseline (Visit 3) to post-treatment (Visit 5) assessed by ambulatory blood pressure monitoring (ABPM) in LPCN 1021 treated adult hypogonadal male subjects.

Detailed Description
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This is an open-label, multi-center, single arm study evaluating the blood pressure (BP) changes from baseline (Visit 3) to post-treatment (Visit 5) assessed by ambulatory blood pressure monitoring (ABPM) in LPCN 1021 treated adult hypogonadal male subjects. The study is comprised of six scheduled visits: Visit 1 and 2 are for screening, Visit 3 is to assess subject's baseline BP and pulse rate (PR) via ABPM. Visit 4 is to enroll subjects, and to provide subjects with study medication for the start of dosing. Visit 5 is to assess subject's post-treatment BP and PR via ABPM. Visit 6 is to perform exit visit procedures.

Official Title
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Ambulatory Blood Pressure Monitoring in Oral Testosterone Undecanoate (TU, LPCN 1021) Treated Hypogonadal Men

Conditions
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Hypogonadism, Male

Intervention / Treatment
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* Drug: LPCN 1021


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily sign and date the study consent form(s) which have been approved by an Institutional Review Board (IRB). Written consent must be obtained prior to the initiation of any study procedures. Male between 18 and 80 years of age, inclusive, with documented onset of hypogonadism prior to age 65. Subjects should be diagnosed to be primary (congenital or acquired) or secondary hypogonadal (congenital or acquired). Serum total T below lab normal range (300 ng/dL) based on two consecutive blood samples obtained between 6 and 10 AM, on two separate days at approximately the same time of day, following an appropriate washout of current androgen replacement therapy, if required. Naïve to androgen replacement or has discontinued current treatment and completed adequate washout of prior androgen therapy. Washout must be completed prior to collection of baseline serum T samples to determine study eligibility. Judged to be in good general health as determined by the investigator at screening. Exclusion Criteria: History of significant sensitivity or allergy to androgens, or product excipients. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to: Hemoglobin < 11.5 g/dL or > 16.5 g/dL Hematocrit < 35% or > 54% Serum transaminases > 2.5 times upper limit of normal Serum bilirubin > 2.0 mg/dL Creatinine > 2.0 mg/dL PSA > 4 ng/mL Prolactin > 17.7 ng/mL. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up. Subjects with screening systolic BP or diastolic BP above 160 mmHg or 100 mmHg, respectively. Subjects with symptoms of moderate to severe benign prostatic hyperplasia. History of seizures or convulsions occurring after age 5, including alcohol or drug withdrawal seizures. History of gastric surgery, cholecystectomy, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption. History of any clinically significant illness, infection, or surgical procedure within 1 month prior to study drug administration. Known tolerability issues with ABPM devices. History of stroke, myocardial infarction, transient ischemic attack, or acute coronary syndrome within the past 5 years. History of long QT syndrome (or QTcB > 450) or unexplained sudden death (including cardiac death) or history of long QT syndrome in a first degree relative (parent, sibling, or child). Subjects who are not on stable dose of current medication (no changes in medication in the last 3 months). History of current or suspected prostate or breast cancer. History of untreated obstructive sleep apnea or not compliant with sleep apnea treatment. Active alcohol or any drug substance abuse, or history of abuse that will interfere with the subject's ability to participate in the study in the judgement of the investigator. Use of known inhibitors (e.g., ketoconazole) or inducers (e.g., dexamethasone, phenytoin, rifampin, carbamazepine) of cytochrome P450 3A (CYP3A) within 30 days prior to study drug administration and through the end of the study. A list of prohibited medications is provided in Appendix C. Use of any investigational drug within 5 half-lives of the last dose in the past 6 months prior to Study Day -2 without principal investigator and/or sponsor approval. Receipt of any investigational drug by injection within 30 days or 10 half-lives (whichever is longer) prior to study drug administration without principal investigator and/or sponsor approval. Subject who is not willing to use adequate contraception for the duration of the study. Any contraindications to a MRI scan (i.e. subjects with non-removable ferromagnetic implants, pacemakers, aneurysm clips or other foreign bodies), and/or subjects with claustrophobic symptoms and/or inability to fit into an MRI scanner. Inability to understand and provide written informed consent for the study. Considered by the investigator or the sponsor-designated physician, for any reason, that the subject is an unsuitable candidate to receive LPCN 1021 (exact reason should be specified by the investigator).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LPCN 1021<br>LPCN 1021 at a 225 mg dose taken twice daily (total daily dose of 450 mg taken as 225 mg in the morning and 225 mg in the evening), | Drug: LPCN 1021<br>* LPCN 1021 is gelatin capsule product provided as 112.5 mg testosterone undecanoate per capsule.<br>* Other names: TLANDO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ambulatory Blood Pressure Monitoring (ABPM)-Measured Average 24-hour Systolic Blood Pressure (SBP) | Change in average systolic blood pressure as measured by ambulatory blood pressure monitoring (ABPM) from Visit 3 (Baseline) to Visit 5 (End of Study) | Baseline to end of study (approximately 4 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ABPM-measured Average Daytime SBP | Change in average daytime SBP as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average Nighttime SBP | Change in average nighttime SBP as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average 24-hour Diastolic Blood Pressure (DBP) | Change in average 24-hour DBP as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average Daytime DBP | Change in average daytime DBP as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average Nighttime DBP | Change in average nighttime DBP as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average 24-hour Pulse Rate (PR) | Change in average 24-hour pulse rate as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average Daytime PR | Change in average daytime pulse rate as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in ABPM-measured Average Nighttime PR | Change in average nighttime pulse rate as measured by ABPM from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in Morning SBP Measured in Triplicate at the Clinic | Change in morning systolic blood pressure measured in triplicate at the clinic from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in Morning DBP Measured in Triplicate at the Clinic | Change in morning diastolic blood pressure measured in triplicate at the clinic from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in Morning PR Measured in Triplicate at the Clinic | Change in morning pulse rate measured in triplicate at the clinic from Visit 3 to Visit 5 | Baseline to End of Study (approximately 4 months) | 
| Change in Patient Reported Sexual Distress | Change in patient reported sexual distress from visit 3 to Visit 5 Female Sexual Distress Scale - Revised, Item 13 Possible scores range from 0 (better) to 4 (worse) | Baseline to End of Study (approximately 4 months) | 
| Change in Patient Reported Sexual Desire | Change in patient reported sexual desire from visit 3 to Visit 5 Psychosexual Daily Questionnaire Possible scores range from 0 (worse) to 5 (better) | Baseline to End of Study (approximately 4 months) | 
| Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Interim Analysis (MRI-2)- Subgroup: MRI-PDFF of ≥5% | Percent Relative Change in Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) from Baseline (MRI-1) to Interim Analysis (MRI-2) in subjects with a baseline MRI-PDFF of ≥5% | Baseline (MRI-1) to Interim Analysis (MRI-2) (Approximately 8 Weeks) | 
| Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Post-Treatment Analysis (MRI-3)- Subgroup: MRI-PDFF of ≥5% | Percent Relative Change in Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) from Baseline (MRI-1) to Post-Treatment Analysis (MRI-3) in subjects with a baseline MRI-PDFF of ≥5% | Baseline (MRI-1) to Post-Treatment Analysis (MRI-3) (Approximately 16 Weeks) | 
| Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Interim Analysis (MRI-2)- Subgroup: MRI-PDFF of ≥10% | Percent Relative Change in Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) from Baseline (MRI-1) to Interim Analysis (MRI-2) in subjects with a baseline MRI-PDFF of ≥10% | Baseline (MRI-1) to Interim Analysis (MRI-2) (Approximately 8 Weeks) | 
| Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Post-Treatment Analysis (MRI-3)- Subgroup: MRI-PDFF of ≥10% | Percent Relative Change in Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) from Baseline (MRI-1) to Post-Treatment Analysis (MRI-3) in subjects with a baseline MRI-PDFF of ≥10% | Baseline (MRI-1) to Post-Treatment Analysis (MRI-3) (Approximately 16 Weeks) |