Clinical trial NCT03868059: Ambulatory Blood Pressure Monitoring in Oral Testosterone Undecanoate (TU, LPCN 1021) Treated Hypogonadal Men
Official title: Ambulatory Blood Pressure Monitoring in Oral Testosterone Undecanoate (TU, LPCN 1021) Treated Hypogonadal Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypogonadism, Male
Lead sponsor: Lipocine Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-08
Enrollment: 138
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Ambulatory Blood Pressure Monitoring (ABPM)-Measured Average 24-hour Systolic Blood Pressure (SBP)
timeFrame: Baseline to end of study (approximately 4 months).
Secondary outcomes:
measure: Change in ABPM-measured Average Daytime SBP
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average Nighttime SBP
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average 24-hour Diastolic Blood Pressure (DBP)
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average Daytime DBP
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average Nighttime DBP
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average 24-hour Pulse Rate (PR)
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average Daytime PR
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average Nighttime PR
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Morning SBP Measured in Triplicate at the Clinic
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Morning DBP Measured in Triplicate at the Clinic
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Morning PR Measured in Triplicate at the Clinic
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Patient Reported Sexual Distress
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Patient Reported Sexual Desire
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Interim Analysis (MRI-2)- Subgroup: MRI-PDFF of ≥5%
timeFrame: Baseline (MRI-1) to Interim Analysis (MRI-2) (Approximately 8 Weeks)
measure: Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Post-Treatment Analysis (MRI-3)- Subgroup: MRI-PDFF of ≥5%
timeFrame: Baseline (MRI-1) to Post-Treatment Analysis (MRI-3) (Approximately 16 Weeks)
measure: Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Interim Analysis (MRI-2)- Subgroup: MRI-PDFF of ≥10%
timeFrame: Baseline (MRI-1) to Interim Analysis (MRI-2) (Approximately 8 Weeks)
measure: Percent Relative Change in MRI-PDFF From Baseline (MRI-1) to Post-Treatment Analysis (MRI-3)- Subgroup: MRI-PDFF of ≥10%
timeFrame: Baseline (MRI-1) to Post-Treatment Analysis (MRI-3) (Approximately 16 Weeks)
Other outcomes:
measure: Change is SBP Dip
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average 24-hour SBP in Subjects With a Low Framingham Risk Score (FRS)
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average 24-hour SBP in Subjects With a Moderate Framingham Risk Score (FRS)
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average 24-hour SBP in Subjects With a High Framingham Risk Score (FRS)
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in ABPM-measured Average 24-hour SBP in Subjects With a Baseline SBP >140mmHg
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Hematocrit From Baseline
timeFrame: Baseline to end of Study (approximately 4 months)
measure: Number of Participants Who Started a New Hypertensive Medication or Increased Their Hypertensive Medication Dose
timeFrame: Baseline to End of Study (approximately 4 months)
measure: Change in Hemoglobin From Baseline
timeFrame: Baseline to End of Study (approximately 4 months)
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics
state: Alabama
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Hialeah
country: United States
facility: Neostart Corporation dba AGA Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Impotence Treatment Center
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research, LLC
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: Shreveport
country: United States
facility: Regional Urology
state: Louisiana
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: New York
country: United States
facility: Manhattan Medical Research Practice PLLC
state: New York
city: Columbus
country: United States
facility: Aventiv Research, Inc.
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: West Valley City
country: United States
facility: Granger Medical Clinic
state: Utah
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
Study officials:
affiliation: Lipocine Inc.
name: Anthony Delconte, MD
role: STUDY_DIRECTOR
References:
citation: 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.