Open-Label Study, Evaluating Patient Satisfaction and Symptom Improvement When Treating Male Hypogonadism With Natesto™
Condition: Hypogonadism
MeSH terms: Hypogonadism
Study type: Interventional
Phase: Phase 4

Summary: 
      Multicenter study consisting of two study periods as follows: a 90-day Treatment Period, with
      potential extension by 30 days for those patients requiring a dose increase, as determined by
      the treating physician. Participants receiving 122.5mg of NATESTO (5.5 mg of testosterone)
      per nostril twice daily may have an increased daily dose adjustment on Day 90, based on their
      hypogonadism symptoms.
    

Detailed description: 
      The primary objective of the study is to measure patient satisfaction with testosterone
      replacement therapy before (for non-naïve patients), during and after treatment with NATESTO.

      The secondary objectives of this study are to evaluate the following:

        -  Improvement in hypogonadism symptoms;

        -  Patient treatment preference versus prior testosterone replacement therapy;

        -  Frequency of daily dose of NATESTO;

        -  Safety monitoring.

      The population for this study is adult men 18-65 years of age inclusive, with primary or
      secondary hypogonadism, with historical documented total serum testosterone concentration of
      ≤300 ng/dL and the ability to provide informed consent. Eligible subjects include
      treatment-naïve, hypogonadal patients with a documented confirmation of hypogonadism, as well
      as patients previously treated with an alternate topical testosterone replacement therapy
      (TRT) for at least three months prior to selection. Participants currently receiving topical
      testosterone replacement therapy will be required to discontinue their current testosterone
      treatment before initiating treatment with NATESTO. The approximate total duration of study
      participation for participants completing the study will be up to 150 days (~21 weeks).

      This is a Phase 4, multicenter study consisting of two study periods as follows:

        -  A 90-day Treatment Period, extended to 120-days for those subjects requiring a dose
           increase, during which participants will receive 122.5 mg of NATESTO (5.5mg
           testosterone) per nostril twice daily (BID) for 90 days. At Day 90, the treating
           physician will assess the patient's hypogonadism symptoms, review patient's completed
           questionnaires and based on the Canadian Men's Health Foundation Multidisciplinary
           Guidelines as endorsed by both the Canadian Urological Association and the Canadian
           Society of Endocrinology and Metabolism1, decide if continuation at a higher dose
           frequency of three-times daily (TID) is required for efficacy. For TID patients, there
           will be a 30-day Treatment Extension during which participants whose symptoms were not
           adequately treated on a BID dose, will receive 122.5 mg of NATESTO TID (5.5mg
           testosterone) per nostril. At Day 120, the TID patient will return to the site for
           examination, discussion of symptoms with the physician and questionnaire completion. All
           patients will have their blood testosterone levels assessed at Day 90 and only TID
           patients at Day 120.

        -  Post-study follow-up: All study patients will be requested to follow up at Day 150 to
           confirm whether they continued therapy with NATESTO.

      Patient selection will come as a result of a doctor's visit for routine controls,
      prescription renewal and by pre-selection by the physician from among hypogonadal patients
      currently receiving topical testosterone replacement therapies and willing to participate in
      a clinical trial with NATESTO, or as a result of an initial consultation for naïve patients.

      At Visit 1, patients who agree to participate in the study will come to the site. They will
      provide written informed consent and undergo a complete physical examination, including a
      nasal examination, and medical history collection. Blood pressure, heart rate, weight, and
      height measurements (from which body mass index [BMI] will be determined) will also be
      performed. Blood will be drawn at a local lab for safety assessment. However, if these values
      have already been documented in their patient file from the preceding 6 months, then those
      values will be entered into the eCRF. Previous treatment for hypogonadism (drug and nondrug;
      daily dose) will be recorded, as well as other concomitant treatment with drug or nondrug
      therapies. Study questionnaires Treatment Satisfaction Questionnaire for Medication (TSQM)
      and quantitative Androgen Deficiency in the Aging Male (qADAM) will be reviewed and subjects
      will be given instructions for proper completion of the instruments. Patients will complete
      Part A of the Patient Preference and Use Questionnaire. Patients will also be provided with a
      prescription for a 90-day supply of the study medication, NATESTO, and a Study Drug Access
      Card that will be used for payment purposes at the patient's preferred pharmacy.

      Non-naïve participants will be instructed to stop their current topical treatment at least
      one day and no more than 7 days prior to initiation of treatment with NATESTO. Patients
      should not take both medications simultaneously.

      The open-label Treatment Period will consist of a maximum of 5 study visits: 2 visits will be
      done via telephone by the Study Coordinator (Visit 2, Day 30 and Visit 3, Day 60) and one
      clinic visit (Visit 4, Day 90), and a last clinic visit for patients who were placed on a TID
      dose (Visit 5, Day 120).

      At Visit 2 (Day 30) and Visit 3 (Day 60), participants will be required to complete
      questionnaires (TSQM and qADAM) by telephone with the Study Coordinator, and will also be
      asked about any concurrent medications or AEs.

      At Visit 4 (Day 90), the patient will return to the site. Any unreported adverse events will
      be recorded. Patients will undergo a basic physical examination including a nasal
      examination. Blood pressure, heart rate, weight, and height measurements (from which body
      mass index [BMI] will be determined) will be recorded. Hypogonadism symptoms will be assessed
      by the Investigator making reference to the qADAM questionnaire results, and the patient will
      complete the TSQM.

      At Visit 4 (Day 90), if in the physician's judgment the patient is adequately treated with
      twice daily (BID) NATESTO, the physician will decide whether the patient a.) should return to
      their previous therapy; b.) remain on NATESTO; or c.) consider a new treatment option. The
      physician will provide the patient with a prescription for the treatment chosen. The BID
      patients will have a blood draw taken at a local laboratory for safety assessment and to
      assess their testosterone level. This will constitute the END OF TREATMENT for BID subjects.
      These adequately controlled patients will complete Part B (for Non-naïve) or Part C (for
      Naïve) of the Patient Preference and Use Questionnaire.

      At Visit 4 (Day 90), if the physician's judgement is that the twice daily (BID) dose of
      NATESTO was not adequate to treat the patient's symptoms and believes that the patient will
      benefit from a higher dose, then a prescription will be given to the patient for three times
      daily (TID) NATESTO. The Study Drug Access Card will be used for payment purposes at the
      patient's preferred pharmacy. These patients moving to TID will have a blood draw taken at a
      local laboratory to assess safety as well as their testosterone level. The patient will
      schedule Visit 5 (Day 120) at this time.

      At Visit 5 (Day 120 for TID patients only), any unreported adverse events will be recorded.
      Patients will undergo a basic physical examination including a nasal examination. Blood
      pressure, heart rate, weight, and height measurements (from which body mass index [BMI] will
      be determined) will be recorded. The patients will have a blood draw taken at a local
      laboratory for safety assessment and to assess their testosterone level. In addition to TSQM
      and qADAM questionnaires, subjects will also complete Part B (for Non-naïve) or Part C (for
      Naïve) of the Patient Preference and Use Questionnaire. The physician will decide whether the
      patient a.) should return to their previous therapy; b.) remain on NATESTO; or c.) consider a
      new treatment option. The physician will provide the patient with a prescription for the
      treatment chosen.

      At Visit 6 (Day 150), all study patients will be asked by telephone whether they are still
      taking NATESTO and why (or why not).
    

Intervention name(s): NATESTO Testosterone Nasal Gel
Intervention type(s): Drug
Intervention description(s): Participants will be instructed to administer 5.5 mg of testosterone (1 actuation) per nostril of NATESTO Testosterone Nasal Gel once in the morning and once in the evening (at least 6 hours apart), preferably at the same time each day for a total daily dose of 22 mg/day of testosterone. Patients should be instructed to completely depress the pump 1 time in each nostril to receive the total dose.
For three times daily (after Visit 4 [Day 90] if symptoms not adequately managed by a BID dose), NATESTO will be administered intranasally once in the morning, once in the afternoon and once in the evening (approximately 6-8 hours apart), preferably at the same time each day for a total daily dose of 33 mg/day of testosterone.
Other intervention name(s): NATESTO
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hypogonadism