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

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.

Study Overview

• Status: Completed
• Conditions: Hypogonadism, Male
• Intervention / Treatment: Drug: LPCN 1021

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Hialeah, Florida, United States, 33012
      • Neostart Corporation dba AGA Clinical Trials
    • Jacksonville, Florida, United States, 32223
      • Jacksonville Impotence Treatment Center
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research, LLC
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center of Florida
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology
  • New York
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • New York, New York, United States, 10016
      • Manhattan Medical Research Practice PLLC
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc.
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Utah
    • West Valley City, Utah, United States, 84096
      • Granger Medical Clinic
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. 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.
2. Male between 18 and 80 years of age, inclusive, with documented onset of hypogonadism prior to age 65.
3. Subjects should be diagnosed to be primary (congenital or acquired) or secondary hypogonadal (congenital or acquired).
4. 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.
5. 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.
6. Judged to be in good general health as determined by the investigator at screening.

Exclusion Criteria:

1. History of significant sensitivity or allergy to androgens, or product excipients.

2. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to:

   1. Hemoglobin < 11.5 g/dL or > 16.5 g/dL
   2. Hematocrit < 35% or > 54%
   3. Serum transaminases > 2.5 times upper limit of normal
   4. Serum bilirubin > 2.0 mg/dL
   5. Creatinine > 2.0 mg/dL
   6. PSA > 4 ng/mL
   7. Prolactin > 17.7 ng/mL.
3. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up.
4. Subjects with screening systolic BP or diastolic BP above 160 mmHg or 100 mmHg, respectively.
5. Subjects with symptoms of moderate to severe benign prostatic hyperplasia.
6. History of seizures or convulsions occurring after age 5, including alcohol or drug withdrawal seizures.
7. History of gastric surgery, cholecystectomy, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.
8. History of any clinically significant illness, infection, or surgical procedure within 1 month prior to study drug administration.
9. Known tolerability issues with ABPM devices.
10. History of stroke, myocardial infarction, transient ischemic attack, or acute coronary syndrome within the past 5 years.
11. 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).
12. Subjects who are not on stable dose of current medication (no changes in medication in the last 3 months).
13. History of current or suspected prostate or breast cancer.
14. History of untreated obstructive sleep apnea or not compliant with sleep apnea treatment.
15. 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.
16. 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.
17. 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.
18. 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.
19. Subject who is not willing to use adequate contraception for the duration of the study.
20. 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.
21. Inability to understand and provide written informed consent for the study.
22. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LPCN 1021; 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; LPCN 1021 is gelatin capsule product provided as 112.5 mg testosterone undecanoate per capsule.; Other Names: TLANDO

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change is SBP Dip	Change in systolic blood pressure dip, as defined as the difference between daytime mean systolic blood pressure and nighttime mean systolic blood pressure, from Visit 3 to Visit 5	Baseline to End of Study (approximately 4 months)
Change in ABPM-measured Average 24-hour SBP in Subjects With a Low Framingham Risk Score (FRS)	Change in average 24-hour SBP in subjects with a low cardiovascular risk based on their Framingham Risk Score (0<FRS<11) from Visit 3 (Baseline) to Visit 5 (End of Study); Risk Level: Low: 0<FRS<11; Moderate: 11≤FRS<24; High: FRS≥24.	Baseline to End of Study (approximately 4 months)
Change in ABPM-measured Average 24-hour SBP in Subjects With a Moderate Framingham Risk Score (FRS)	Change in average 24-hour SBP in subjects with a moderate cardiovascular risk based on their Framingham Risk Score (11≤FRS<24) from Visit 3 (Baseline) to Visit 5 (End of Study); Risk Level: Low: 0<FRS<11; Moderate: 11≤FRS<24; High: FRS≥24.	Baseline to End of Study (approximately 4 months)
Change in ABPM-measured Average 24-hour SBP in Subjects With a High Framingham Risk Score (FRS)	Change in average 24-hour SBP in subjects with a high cardiovascular risk based on their Framingham Risk Score (FRS≥24) from Visit 3 (Baseline) to Visit 5 (End of Study); Risk Level: Low: 0<FRS<11; Moderate: 11≤FRS<24; High: FRS≥24.	Baseline to End of Study (approximately 4 months)
Change in ABPM-measured Average 24-hour SBP in Subjects With a Baseline SBP >140mmHg	Change in average 24-hour SBP as measured by ABPM in subjects with a baseline SBP >140mmHg from Visit 3 to Visit 5	Baseline to End of Study (approximately 4 months)
Change in Hematocrit From Baseline	Change in Hematocrit (%) from Visit 3 to Visit 5	Baseline to end of Study (approximately 4 months)
Number of Participants Who Started a New Hypertensive Medication or Increased Their Hypertensive Medication Dose	Number of participants who had to start a new hypertensive medication or increase their hypertensive medication dose from Visit 3 to Visit 5	Baseline to End of Study (approximately 4 months)
Change in Hemoglobin From Baseline	Change in Hemoglobin from Visit 3 to Visit 5	Baseline to End of Study (approximately 4 months)

Collaborators and Investigators

• Sponsor: Lipocine Inc.

Publications and helpful links

General Publications

• White WB, Dobs A, Carson C, DelConte A, Khera M, Miner M, Shahid M, Kim K, Chidambaram N. Effects of a Novel Oral Testosterone Undecanoate on Ambulatory Blood Pressure in Hypogonadal Men. J Cardiovasc Pharmacol Ther. 2021 Nov;26(6):630-637. doi: 10.1177/10742484211027394. Epub 2021 Jun 30.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 30, 2018
• Primary Completion (ACTUAL): February 19, 2019
• Study Completion (ACTUAL): February 21, 2019

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: March 7, 2019
• First Posted (ACTUAL): March 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Eunuchism; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: LPCN 1021-18-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No