Trial Outcomes & Findings for Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension (NCT NCT01515865)

NCT ID: NCT01515865

Last Updated: 2021-06-09

Results Overview

Failure to maintain a response was defined as any randomized subject that met both criterion 1 and criterion 2 below on Day 16: 1. The Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 score increased by \>=4 points compared to baseline. OHSA Item 1 is a dizziness scale that is scored on a range from 0 (no dizziness) to 10 (severe dizziness). A lower score indicates less severe symptoms. 2. There was an increase in the number of syncopal/near syncopal events or severity of events within 15 minutes of standing compared to those observed at baseline. Syncope was defined as a loss of consciousness, and near syncope was defined as a feeling (e.g., dizziness, lightheadedness, feeling faint, feeling as though one would black out) that, without intervention, would lead to a loss of consciousness.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 98 participants
• Primary outcome timeframe: 30 minutes post-dose on Day 16
• Results posted on: 2021-06-09

Participant Flow

Subjects received the dose and frequency of Midodrine HCl that they had been receiving during their non-study treatment prior to enrolling in this study.

Participant milestones

Measure	Midodrine HCl - (Open-label) On the morning of Day -1, subjects took their usual morning dose of midodrine HCl, using their own midodrine HCl supplies at approximately the same time before rising that they would normally take their morning dose. On the morning of Day 1, subjects had their usual morning dose of midodrine HCl withheld. On Day 2, all eligible subjects continued on their midodrine HCl dose regimen over at least 14 days, using study-supplied investigational product.	Midodrine HCl - (Randomized) On Day 16 subjects received over-encapsulated midodrine HCl tablets (equivalent to their previously prescribed dose).	Placebo - (Randomized) On Day 16 subjects received matching placebo.
Part A (Open-label) STARTED	98	0	0
Part A (Open-label) COMPLETED	95	0	0
Part A (Open-label) NOT COMPLETED	3	0	0
Part B (Open-label) STARTED	71	0	0
Part B (Open-label) COMPLETED	69	0	0
Part B (Open-label) NOT COMPLETED	2	0	0
Part C (Randomized) STARTED	0	33	34
Part C (Randomized) COMPLETED	0	33	34
Part C (Randomized) NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Midodrine HCl - (Open-label) On the morning of Day -1, subjects took their usual morning dose of midodrine HCl, using their own midodrine HCl supplies at approximately the same time before rising that they would normally take their morning dose. On the morning of Day 1, subjects had their usual morning dose of midodrine HCl withheld. On Day 2, all eligible subjects continued on their midodrine HCl dose regimen over at least 14 days, using study-supplied investigational product.	Midodrine HCl - (Randomized) On Day 16 subjects received over-encapsulated midodrine HCl tablets (equivalent to their previously prescribed dose).	Placebo - (Randomized) On Day 16 subjects received matching placebo.
Part A (Open-label) Other	3	0	0
Part B (Open-label) Withdrawal by Subject	1	0	0
Part B (Open-label) Other	1	0	0

Baseline Characteristics

Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension

Baseline characteristics by cohort

Measure	Enrolled Population n=98 Participants
Age, Continuous	45.5 years STANDARD_DEVIATION 17.45 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Region of Enrollment United States	90 Participants n=5 Participants
Region of Enrollment Slovakia	3 Participants n=5 Participants
Region of Enrollment Poland	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes post-dose on Day 16

Population: The Full Analysis Set was defined as all randomized subjects who received at least 1 dose of double-blind investigational product.

Failure to maintain a response was defined as any randomized subject that met both criterion 1 and criterion 2 below on Day 16: 1. The Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 score increased by >=4 points compared to baseline. OHSA Item 1 is a dizziness scale that is scored on a range from 0 (no dizziness) to 10 (severe dizziness). A lower score indicates less severe symptoms. 2. There was an increase in the number of syncopal/near syncopal events or severity of events within 15 minutes of standing compared to those observed at baseline. Syncope was defined as a loss of consciousness, and near syncope was defined as a feeling (e.g., dizziness, lightheadedness, feeling faint, feeling as though one would black out) that, without intervention, would lead to a loss of consciousness.

Outcome measures

Measure	Midodrine HCl n=33 Participants Over-encapsulated midodrine HCl tablet at the subjects previously prescribed dose level.	Placebo n=34 Participants Matching placebo treatment (utilizing the same number of placebo capsules that would be required to constitute their midodrine HCl dose).
Percent of Subjects Who Failed to Maintain a Response	30.3 percentage of participants	44.1 percentage of participants

Adverse Events

Midodrine HCl - Open-label (Part A)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Midodrine HCl - Open-label (Part B)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Midodrine HCl - Randomized (Part C)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo - Randomized (Part C)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Midodrine HCl - Open-label (Part A) n=98 participants at risk dose at the subjects current dose level	Midodrine HCl - Open-label (Part B) n=71 participants at risk open-label study-supplied (Part B) dose at subjects current dose level	Midodrine HCl - Randomized (Part C) n=33 participants at risk over-encapsulated randomized dose (Part C) at subjects current dose level	Placebo - Randomized (Part C) n=34 participants at risk over-encapsulated randomized matching placebo
Nervous system disorders Headache	5.1% 5/98 • Number of events 5	2.8% 2/71 • Number of events 2	0.00% 0/33	0.00% 0/34

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER